Phenome-Wide Association Studies as a Tool to Advance Precision Medicine

PubMed Central

Denny, Joshua C.; Bastarache, Lisa; Roden, Dan M.

2017-01-01

Beginning in the early 2000s, the accumulation of biospecimens linked to electronic health records (EHRs) made possible genome-phenome studies (i.e., comparative analyses of genetic variants and phenotypes) using only data collected as a by-product of typical health care. In addition to disease and trait genetics, EHRs proved a valuable resource for analyzing pharmacogenetic traits and developing reverse genetics approaches such as phenome-wide association studies (PheWASs). PheWASs are designed to survey which of many phenotypes may be associated with a given genetic variant. PheWAS methods have been validated through replication of hundreds of known genotype-phenotype associations, and their use has differentiated between true pleiotropy and clinical comorbidity, added context to genetic discoveries, and helped define disease subtypes, and may also help repurpose medications. PheWAS methods have also proven to be useful with research-collected data. Future efforts that integrate broad, robust collection of phenotype data (e.g., EHR data) with purpose-collected research data in combination with a greater understanding of EHR data will create a rich resource for increasingly more efficient and detailed genome-phenome analysis to usher in new discoveries in precision medicine. PMID:27147087

Phenomic approaches and tools for phytopathologists

USDA-ARS?s Scientific Manuscript database

Plant phenomics approaches aim to evaluate traits such as growth, performance, and composition of plants using a suite of non-invasive technologies. The ultimate goal is to link phenotypic traits to the genetic information for particular genotypes, thus creating the bridge between the phenome and ge...

From Genome-Wide Association Study to Phenome-Wide Association Study: New Paradigms in Obesity Research.

PubMed

Zhang, Y-P; Zhang, Y-Y; Duan, D D

2016-01-01

Obesity is a condition in which excess body fat has accumulated over an extent that increases the risk of many chronic diseases. The current clinical classification of obesity is based on measurement of body mass index (BMI), waist-hip ratio, and body fat percentage. However, these measurements do not account for the wide individual variations in fat distribution, degree of fatness or health risks, and genetic variants identified in the genome-wide association studies (GWAS). In this review, we will address this important issue with the introduction of phenome, phenomics, and phenome-wide association study (PheWAS). We will discuss the new paradigm shift from GWAS to PheWAS in obesity research. In the era of precision medicine, phenomics and PheWAS provide the required approaches to better definition and classification of obesity according to the association of obese phenome with their unique molecular makeup, lifestyle, and environmental impact. Copyright © 2016 Elsevier Inc. All rights reserved.

Efficient genome-wide association in biobanks using topic modeling identifies multiple novel disease loci.

PubMed

McCoy, Thomas H; Castro, Victor M; Snapper, Leslie A; Hart, Kamber L; Perlis, Roy H

2017-08-31

Biobanks and national registries represent a powerful tool for genomic discovery, but rely on diagnostic codes that may be unreliable and fail to capture the relationship between related diagnoses. We developed an efficient means of conducting genome-wide association studies using combinations of diagnostic codes from electronic health records (EHR) for 10845 participants in a biobanking program at two large academic medical centers. Specifically, we applied latent Dirichilet allocation to fit 50 disease topics based on diagnostic codes, then conducted genome-wide common-variant association for each topic. In sensitivity analysis, these results were contrasted with those obtained from traditional single-diagnosis phenome-wide association analysis, as well as those in which only a subset of diagnostic codes are included per topic. In meta-analysis across three biobank cohorts, we identified 23 disease-associated loci with p<1e-15, including previously associated autoimmune disease loci. In all cases, observed significant associations were of greater magnitude than for single phenome-wide diagnostic codes, and incorporation of less strongly-loading diagnostic codes enhanced association. This strategy provides a more efficient means of phenome-wide association in biobanks with coded clinical data.

Efficient Genome-wide Association in Biobanks Using Topic Modeling Identifies Multiple Novel Disease Loci

PubMed Central

McCoy, Thomas H; Castro, Victor M; Snapper, Leslie A; Hart, Kamber L; Perlis, Roy H

2017-01-01

Biobanks and national registries represent a powerful tool for genomic discovery, but rely on diagnostic codes that can be unreliable and fail to capture relationships between related diagnoses. We developed an efficient means of conducting genome-wide association studies using combinations of diagnostic codes from electronic health records for 10,845 participants in a biobanking program at two large academic medical centers. Specifically, we applied latent Dirichilet allocation to fit 50 disease topics based on diagnostic codes, then conducted a genome-wide common-variant association for each topic. In sensitivity analysis, these results were contrasted with those obtained from traditional single-diagnosis phenome-wide association analysis, as well as those in which only a subset of diagnostic codes were included per topic. In meta-analysis across three biobank cohorts, we identified 23 disease-associated loci with p < 1e-15, including previously associated autoimmune disease loci. In all cases, observed significant associations were of greater magnitude than single phenome-wide diagnostic codes, and incorporation of less strongly loading diagnostic codes enhanced association. This strategy provides a more efficient means of identifying phenome-wide associations in biobanks with coded clinical data. PMID:28861588

Dynamic Quantitative Trait Locus Analysis of Plant Phenomic Data.

PubMed

Li, Zitong; Sillanpää, Mikko J

2015-12-01

Advanced platforms have recently become available for automatic and systematic quantification of plant growth and development. These new techniques can efficiently produce multiple measurements of phenotypes over time, and introduce time as an extra dimension to quantitative trait locus (QTL) studies. Functional mapping utilizes a class of statistical models for identifying QTLs associated with the growth characteristics of interest. A major benefit of functional mapping is that it integrates information over multiple timepoints, and therefore could increase the statistical power for QTL detection. We review the current development of computationally efficient functional mapping methods which provide invaluable tools for analyzing large-scale timecourse data that are readily available in our post-genome era. Copyright © 2015 Elsevier Ltd. All rights reserved.

The MR-Base platform supports systematic causal inference across the human phenome

PubMed Central

Wade, Kaitlin H; Haberland, Valeriia; Baird, Denis; Laurin, Charles; Burgess, Stephen; Bowden, Jack; Langdon, Ryan; Tan, Vanessa Y; Yarmolinsky, James; Shihab, Hashem A; Timpson, Nicholas J; Evans, David M; Relton, Caroline; Martin, Richard M; Davey Smith, George

2018-01-01

Results from genome-wide association studies (GWAS) can be used to infer causal relationships between phenotypes, using a strategy known as 2-sample Mendelian randomization (2SMR) and bypassing the need for individual-level data. However, 2SMR methods are evolving rapidly and GWAS results are often insufficiently curated, undermining efficient implementation of the approach. We therefore developed MR-Base (http://www.mrbase.org): a platform that integrates a curated database of complete GWAS results (no restrictions according to statistical significance) with an application programming interface, web app and R packages that automate 2SMR. The software includes several sensitivity analyses for assessing the impact of horizontal pleiotropy and other violations of assumptions. The database currently comprises 11 billion single nucleotide polymorphism-trait associations from 1673 GWAS and is updated on a regular basis. Integrating data with software ensures more rigorous application of hypothesis-driven analyses and allows millions of potential causal relationships to be efficiently evaluated in phenome-wide association studies. PMID:29846171

Mimvec: a deep learning approach for analyzing the human phenome.

PubMed

Gan, Mingxin; Li, Wenran; Zeng, Wanwen; Wang, Xiaojian; Jiang, Rui

2017-09-21

The human phenome has been widely used with a variety of genomic data sources in the inference of disease genes. However, most existing methods thus far derive phenotype similarity based on the analysis of biomedical databases by using the traditional term frequency-inverse document frequency (TF-IDF) formulation. This framework, though intuitive, not only ignores semantic relationships between words but also tends to produce high-dimensional vectors, and hence lacks the ability to precisely capture intrinsic semantic characteristics of biomedical documents. To overcome these limitations, we propose a framework called mimvec to analyze the human phenome by making use of the state-of-the-art deep learning technique in natural language processing. We converted 24,061 records in the Online Mendelian Inheritance in Man (OMIM) database to low-dimensional vectors using our method. We demonstrated that the vector presentation not only effectively enabled classification of phenotype records against gene ones, but also succeeded in discriminating diseases of different inheritance styles and different mechanisms. We further derived pairwise phenotype similarities between 7988 human inherited diseases using their vector presentations. With a joint analysis of this phenome with multiple genomic data, we showed that phenotype overlap indeed implied genotype overlap. We finally used the derived phenotype similarities with genomic data to prioritize candidate genes and demonstrated advantages of this method over existing ones. Our method is capable of not only capturing semantic relationships between words in biomedical records but also alleviating the dimensional disaster accompanying the traditional TF-IDF framework. With the approaching of precision medicine, there will be abundant electronic records of medicine and health awaiting for deep analysis, and we expect to see a wide spectrum of applications borrowing the idea of our method in the near future.

Beyond endometriosis GWAS: from Genomics to Phenomics to the Patient

PubMed Central

Zondervan, Krina T.; Rahmioglu, Nilufer; Morris, Andrew P.; Nyholt, Dale R.; Montgomery, Grant W.; Becker, Christian M.; Missmer, Stacey A.

2017-01-01

Endometriosis is a heritable, complex chronic inflammatory disease, for which much of the causal pathogenic mechanism remain unknown. Genome-wide association studies (GWAS) to date have identified 12 single nucleotide polymorphisms or SNPs at 10 independent genetic loci associated with endometriosis. Most of these were more strongly associated with rAFS stage III/IV, rather than I/II. The loci are almost all located in inter-genic regions that are known to play a role in the regulation of expression of target genes yet to be identified. To identify the target genes and pathways perturbed by the implicated variants, studies are required involving functional genomic annotation of the surrounding chromosomal regions, in terms of transcriptor factor binding, epigenetic modification (e.g. DNA methylation and histone modification) sites, as well as their correlation with RNA transcription. These studies need to be conducted in tissue types relevant to endometriosis – in particular endometrium. In addition, to allow biologically and clinically relevant interpretation of molecular profiling data, they need to be combined and correlated with detailed, systematically collected phenotypic information (surgical and clinical). The WERF Endometriosis Phenome and Biobanking Harmonization project (EPHect) is a global standardisation initiative that has produced consensus data and sample collection protocols for endometriosis research. These now pave the way for collaborative studies integrating phenomic with genomic data, to identify informative subtypes of endometriosis that will enhance understanding of the pathogenic mechanisms of the disease and discovery of novel, targeted treatments. PMID:27513026

Recursive expectation-maximization clustering: A method for identifying buffering mechanisms composed of phenomic modules

NASA Astrophysics Data System (ADS)

Guo, Jingyu; Tian, Dehua; McKinney, Brett A.; Hartman, John L.

2010-06-01

Interactions between genetic and/or environmental factors are ubiquitous, affecting the phenotypes of organisms in complex ways. Knowledge about such interactions is becoming rate-limiting for our understanding of human disease and other biological phenomena. Phenomics refers to the integrative analysis of how all genes contribute to phenotype variation, entailing genome and organism level information. A systems biology view of gene interactions is critical for phenomics. Unfortunately the problem is intractable in humans; however, it can be addressed in simpler genetic model systems. Our research group has focused on the concept of genetic buffering of phenotypic variation, in studies employing the single-cell eukaryotic organism, S. cerevisiae. We have developed a methodology, quantitative high throughput cellular phenotyping (Q-HTCP), for high-resolution measurements of gene-gene and gene-environment interactions on a genome-wide scale. Q-HTCP is being applied to the complete set of S. cerevisiae gene deletion strains, a unique resource for systematically mapping gene interactions. Genetic buffering is the idea that comprehensive and quantitative knowledge about how genes interact with respect to phenotypes will lead to an appreciation of how genes and pathways are functionally connected at a systems level to maintain homeostasis. However, extracting biologically useful information from Q-HTCP data is challenging, due to the multidimensional and nonlinear nature of gene interactions, together with a relative lack of prior biological information. Here we describe a new approach for mining quantitative genetic interaction data called recursive expectation-maximization clustering (REMc). We developed REMc to help discover phenomic modules, defined as sets of genes with similar patterns of interaction across a series of genetic or environmental perturbations. Such modules are reflective of buffering mechanisms, i.e., genes that play a related role in the maintenance of physiological homeostasis. To develop the method, 297 gene deletion strains were selected based on gene-drug interactions with hydroxyurea, an inhibitor of ribonucleotide reductase enzyme activity, which is critical for DNA synthesis. To partition the gene functions, these 297 deletion strains were challenged with growth inhibitory drugs known to target different genes and cellular pathways. Q-HTCP-derived growth curves were used to quantify all gene interactions, and the data were used to test the performance of REMc. Fundamental advantages of REMc include objective assessment of total number of clusters and assignment to each cluster a log-likelihood value, which can be considered an indicator of statistical quality of clusters. To assess the biological quality of clusters, we developed a method called gene ontology information divergence z-score (GOid_z). GOid_z summarizes total enrichment of GO attributes within individual clusters. Using these and other criteria, we compared the performance of REMc to hierarchical and K-means clustering. The main conclusion is that REMc provides distinct efficiencies for mining Q-HTCP data. It facilitates identification of phenomic modules, which contribute to buffering mechanisms that underlie cellular homeostasis and the regulation of phenotypic expression.

New approaches to the representation and analysis of phenotype knowledge in human diseases and their animal models.

PubMed

Schofield, Paul N; Sundberg, John P; Hoehndorf, Robert; Gkoutos, Georgios V

2011-09-01

The systematic investigation of the phenotypes associated with genotypes in model organisms holds the promise of revealing genotype-phenotype relations directly and without additional, intermediate inferences. Large-scale projects are now underway to catalog the complete phenome of a species, notably the mouse. With the increasing amount of phenotype information becoming available, a major challenge that biology faces today is the systematic analysis of this information and the translation of research results across species and into an improved understanding of human disease. The challenge is to integrate and combine phenotype descriptions within a species and to systematically relate them to phenotype descriptions in other species, in order to form a comprehensive understanding of the relations between those phenotypes and the genotypes involved in human disease. We distinguish between two major approaches for comparative phenotype analyses: the first relies on evolutionary relations to bridge the species gap, while the other approach compares phenotypes directly. In particular, the direct comparison of phenotypes relies heavily on the quality and coherence of phenotype and disease databases. We discuss major achievements and future challenges for these databases in light of their potential to contribute to the understanding of the molecular mechanisms underlying human disease. In particular, we discuss how the use of ontologies and automated reasoning can significantly contribute to the analysis of phenotypes and demonstrate their potential for enabling translational research.

Finding Our Way through Phenotypes

PubMed Central

Deans, Andrew R.; Lewis, Suzanna E.; Huala, Eva; Anzaldo, Salvatore S.; Ashburner, Michael; Balhoff, James P.; Blackburn, David C.; Blake, Judith A.; Burleigh, J. Gordon; Chanet, Bruno; Cooper, Laurel D.; Courtot, Mélanie; Csösz, Sándor; Cui, Hong; Dahdul, Wasila; Das, Sandip; Dececchi, T. Alexander; Dettai, Agnes; Diogo, Rui; Druzinsky, Robert E.; Dumontier, Michel; Franz, Nico M.; Friedrich, Frank; Gkoutos, George V.; Haendel, Melissa; Harmon, Luke J.; Hayamizu, Terry F.; He, Yongqun; Hines, Heather M.; Ibrahim, Nizar; Jackson, Laura M.; Jaiswal, Pankaj; James-Zorn, Christina; Köhler, Sebastian; Lecointre, Guillaume; Lapp, Hilmar; Lawrence, Carolyn J.; Le Novère, Nicolas; Lundberg, John G.; Macklin, James; Mast, Austin R.; Midford, Peter E.; Mikó, István; Mungall, Christopher J.; Oellrich, Anika; Osumi-Sutherland, David; Parkinson, Helen; Ramírez, Martín J.; Richter, Stefan; Robinson, Peter N.; Ruttenberg, Alan; Schulz, Katja S.; Segerdell, Erik; Seltmann, Katja C.; Sharkey, Michael J.; Smith, Aaron D.; Smith, Barry; Specht, Chelsea D.; Squires, R. Burke; Thacker, Robert W.; Thessen, Anne; Fernandez-Triana, Jose; Vihinen, Mauno; Vize, Peter D.; Vogt, Lars; Wall, Christine E.; Walls, Ramona L.; Westerfeld, Monte; Wharton, Robert A.; Wirkner, Christian S.; Woolley, James B.; Yoder, Matthew J.; Zorn, Aaron M.; Mabee, Paula

2015-01-01

Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility. PMID:25562316

Finding our way through phenotypes.

PubMed

Deans, Andrew R; Lewis, Suzanna E; Huala, Eva; Anzaldo, Salvatore S; Ashburner, Michael; Balhoff, James P; Blackburn, David C; Blake, Judith A; Burleigh, J Gordon; Chanet, Bruno; Cooper, Laurel D; Courtot, Mélanie; Csösz, Sándor; Cui, Hong; Dahdul, Wasila; Das, Sandip; Dececchi, T Alexander; Dettai, Agnes; Diogo, Rui; Druzinsky, Robert E; Dumontier, Michel; Franz, Nico M; Friedrich, Frank; Gkoutos, George V; Haendel, Melissa; Harmon, Luke J; Hayamizu, Terry F; He, Yongqun; Hines, Heather M; Ibrahim, Nizar; Jackson, Laura M; Jaiswal, Pankaj; James-Zorn, Christina; Köhler, Sebastian; Lecointre, Guillaume; Lapp, Hilmar; Lawrence, Carolyn J; Le Novère, Nicolas; Lundberg, John G; Macklin, James; Mast, Austin R; Midford, Peter E; Mikó, István; Mungall, Christopher J; Oellrich, Anika; Osumi-Sutherland, David; Parkinson, Helen; Ramírez, Martín J; Richter, Stefan; Robinson, Peter N; Ruttenberg, Alan; Schulz, Katja S; Segerdell, Erik; Seltmann, Katja C; Sharkey, Michael J; Smith, Aaron D; Smith, Barry; Specht, Chelsea D; Squires, R Burke; Thacker, Robert W; Thessen, Anne; Fernandez-Triana, Jose; Vihinen, Mauno; Vize, Peter D; Vogt, Lars; Wall, Christine E; Walls, Ramona L; Westerfeld, Monte; Wharton, Robert A; Wirkner, Christian S; Woolley, James B; Yoder, Matthew J; Zorn, Aaron M; Mabee, Paula

2015-01-01

Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility.

EuroPhenome and EMPReSS: online mouse phenotyping resource

PubMed Central

Mallon, Ann-Marie; Hancock, John M.

2008-01-01

EuroPhenome (http://www.europhenome.org) and EMPReSS (http://empress.har.mrc.ac.uk/) form an integrated resource to provide access to data and procedures for mouse phenotyping. EMPReSS describes 96 Standard Operating Procedures for mouse phenotyping. EuroPhenome contains data resulting from carrying out EMPReSS protocols on four inbred laboratory mouse strains. As well as web interfaces, both resources support web services to enable integration with other mouse phenotyping and functional genetics resources, and are committed to initiatives to improve integration of mouse phenotype databases. EuroPhenome will be the repository for a recently initiated effort to carry out large-scale phenotyping on a large number of knockout mouse lines (EUMODIC). PMID:17905814

EuroPhenome and EMPReSS: online mouse phenotyping resource.

PubMed

Mallon, Ann-Marie; Blake, Andrew; Hancock, John M

2008-01-01

EuroPhenome (http://www.europhenome.org) and EMPReSS (http://empress.har.mrc.ac.uk/) form an integrated resource to provide access to data and procedures for mouse phenotyping. EMPReSS describes 96 Standard Operating Procedures for mouse phenotyping. EuroPhenome contains data resulting from carrying out EMPReSS protocols on four inbred laboratory mouse strains. As well as web interfaces, both resources support web services to enable integration with other mouse phenotyping and functional genetics resources, and are committed to initiatives to improve integration of mouse phenotype databases. EuroPhenome will be the repository for a recently initiated effort to carry out large-scale phenotyping on a large number of knockout mouse lines (EUMODIC).

Size matters: How population size influences genotype–phenotype association studies in anonymized data

PubMed Central

Denny, Joshua C.; Haines, Jonathan L.; Roden, Dan M.; Malin, Bradley A.

2014-01-01

Objective Electronic medical records (EMRs) data is increasingly incorporated into genome-phenome association studies. Investigators hope to share data, but there are concerns it may be “re-identified” through the exploitation of various features, such as combinations of standardized clinical codes. Formal anonymization algorithms (e.g., k-anonymization) can prevent such violations, but prior studies suggest that the size of the population available for anonymization may influence the utility of the resulting data. We systematically investigate this issue using a large-scale biorepository and EMR system through which we evaluate the ability of researchers to learn from anonymized data for genome- phenome association studies under various conditions. Methods We use a k-anonymization strategy to simulate a data protection process (on data sets containing clinical codes) for resources of similar size to those found at nine academic medical institutions within the United States. Following the protection process, we replicate an existing genome-phenome association study and compare the discoveries using the protected data and the original data through the correlation (r2) of the p-values of association significance. Results Our investigation shows that anonymizing an entire dataset with respect to the population from which it is derived yields significantly more utility than small study-specific datasets anonymized unto themselves. When evaluated using the correlation of genome-phenome association strengths on anonymized data versus original data, all nine simulated sites, results from largest-scale anonymizations (population ∼ 100;000) retained better utility to those on smaller sizes (population ∼ 6000—75;000). We observed a general trend of increasing r2 for larger data set sizes: r2 = 0.9481 for small-sized datasets, r2 = 0.9493 for moderately-sized datasets, r2 = 0.9934 for large-sized datasets. Conclusions This research implies that regardless of the overall size of an institution's data, there may be significant benefits to anonymization of the entire EMR, even if the institution is planning on releasing only data about a specific cohort of patients. PMID:25038554

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vogel, John P.

The goal of this project was to apply high-throughput, non-destructive phenotyping (phenomics) to collections of natural variants and induced mutants of the model grass Brachypodium distachyon and characterize a small subset of that material in detail. B. distachyon is well suited to this phenomic approach because its small size and rapid generation time allow researchers to grow many plants under carefully controlled conditions. In addition, the simple diploid genetics, high quality genome sequence and existence of numerous experimental tools available for B. distachyon allow us to rapidly identify genes affecting specific phenotypes. Our phenomic analysis revealed great diversity in biofuel-relevantmore » traits like growth rate, biomass and photosynthetic rate. This clearly demonstrated the feasibility of applying a phenomic approach to the model grass B. distachyon. We also demonstrated the utility of B. distachyon for studying mature root system, something that is virtually impossible to do with biomass crops. We showed tremendous natural variation in root architecture that can potentially be used to design crops with superior nutrient and water harvesting capability. Finally, we demonstrated the speed with which we can link specific genes to specific phenotypes by studying two mutants in detail. Importantly, in both cases, the specific biological lessons learned were grass-specific and could not have been learned from a dicot model system. Furthermore, one of the genes affects cell wall integrity and thus may be a useful target in the context of biomass crop improvement. Ultimately, all this information can be used to accelerate the creation of improved biomass crops.« less

RASopathies: Presentation at the Genome, Interactome, and Phenome Levels.

PubMed

Pevec, Urska; Rozman, Neva; Gorsek, Blaz; Kunej, Tanja

2016-05-01

Clinical symptoms often reflect molecular correlations between mutated proteins. Alignment between interactome and phenome levels reveals new disease genes and connections between previously unrelated diseases. Despite a great potential for novel discoveries, this approach is still rarely used in genomics. In the present study, we analyzed the data of 6 syndromes belonging to the RASopathy class of disorders (RASopathies) and presented them as a model to study associations between genome, interactome, and phenome levels. Causative genes and clinical symptoms were collected from OMIM and NCBI GeneReviews databases for 6 syndromes: Noonan, Noonan syndrome with multiple lentigines, neurofibromatosis type 1, cardiofaciocutaneous, and Legius and Costello syndrome. The STRING tool was used for the identification of protein interactions. Six RASopathy syndromes were found to be associated with 12 causative genes. We constructed an interactome of RASopathy proteins and their neighbors and developed a database of 328 clinical symptoms. The collected data was presented at genome, interactome, and phenome levels and as an integrated network of all 3 data types. The present study provides a baseline for future studies of associations between interactome and phenome in RASopathies and could serve as a novel approach to analyze phenotypically and genetically related diseases.

PhenomeCentral: A Portal for Phenotypic and Genotypic Matchmaking of Patients with Rare Genetic Diseases

PubMed Central

Buske, Orion J.; Girdea, Marta; Dumitriu, Sergiu; Gallinger, Bailey; Hartley, Taila; Trang, Heather; Misyura, Andriy; Friedman, Tal; Beaulieu, Chandree; Bone, William P.; Links, Amanda E.; Washington, Nicole L.; Haendel, Melissa A.; Robinson, Peter N.; Boerkoel, Cornelius F.; Adams, David; Gahl, William A.; Boycott, Kym M.; Brudno, Michael

2017-01-01

The discovery of disease-causing mutations typically requires confirmation of the variant or gene in multiple unrelated individuals, and a large number of rare genetic diseases remain unsolved due to difficulty identifying second families. To enable the secure sharing of case records by clinicians and rare disease scientists, we have developed the PhenomeCentral portal (https://phenomecentral.org). Each record includes a phenotypic description and relevant genetic information (exome or candidate genes). PhenomeCentral identifies similar patients in the database based on semantic similarity between clinical features, automatically prioritized genes from whole-exome data, and candidate genes entered by the users, enabling both hypothesis-free and hypothesis-driven matchmaking. Users can then contact other submitters to follow up on promising matches. PhenomeCentral incorporates data for over 1,000 patients with rare genetic diseases, contributed by the FORGE and Care4Rare Canada projects, the US NIH Undiagnosed Diseases Program, the EU Neuromics and ANDDIrare projects, as well as numerous independent clinicians and scientists. Though the majority of these records have associated exome data, most lack a molecular diagnosis. PhenomeCentral has already been used to identify causative mutations for several patients, and its ability to find matching patients and diagnose these diseases will grow with each additional patient that is entered. PMID:26251998

Scan-o-matic: High-Resolution Microbial Phenomics at a Massive Scale

PubMed Central

Zackrisson, Martin; Hallin, Johan; Ottosson, Lars-Göran; Dahl, Peter; Fernandez-Parada, Esteban; Ländström, Erik; Fernandez-Ricaud, Luciano; Kaferle, Petra; Skyman, Andreas; Stenberg, Simon; Omholt, Stig; Petrovič, Uroš; Warringer, Jonas; Blomberg, Anders

2016-01-01

The capacity to map traits over large cohorts of individuals—phenomics—lags far behind the explosive development in genomics. For microbes, the estimation of growth is the key phenotype because of its link to fitness. We introduce an automated microbial phenomics framework that delivers accurate, precise, and highly resolved growth phenotypes at an unprecedented scale. Advancements were achieved through the introduction of transmissive scanning hardware and software technology, frequent acquisition of exact colony population size measurements, extraction of population growth rates from growth curves, and removal of spatial bias by reference-surface normalization. Our prototype arrangement automatically records and analyzes close to 100,000 growth curves in parallel. We demonstrate the power of the approach by extending and nuancing the known salt-defense biology in baker’s yeast. The introduced framework represents a major advance in microbial phenomics by providing high-quality data for extensive cohorts of individuals and generating well-populated and standardized phenomics databases PMID:27371952

PRECOG: a tool for automated extraction and visualization of fitness components in microbial growth phenomics.

PubMed

Fernandez-Ricaud, Luciano; Kourtchenko, Olga; Zackrisson, Martin; Warringer, Jonas; Blomberg, Anders

2016-06-23

Phenomics is a field in functional genomics that records variation in organismal phenotypes in the genetic, epigenetic or environmental context at a massive scale. For microbes, the key phenotype is the growth in population size because it contains information that is directly linked to fitness. Due to technical innovations and extensive automation our capacity to record complex and dynamic microbial growth data is rapidly outpacing our capacity to dissect and visualize this data and extract the fitness components it contains, hampering progress in all fields of microbiology. To automate visualization, analysis and exploration of complex and highly resolved microbial growth data as well as standardized extraction of the fitness components it contains, we developed the software PRECOG (PREsentation and Characterization Of Growth-data). PRECOG allows the user to quality control, interact with and evaluate microbial growth data with ease, speed and accuracy, also in cases of non-standard growth dynamics. Quality indices filter high- from low-quality growth experiments, reducing false positives. The pre-processing filters in PRECOG are computationally inexpensive and yet functionally comparable to more complex neural network procedures. We provide examples where data calibration, project design and feature extraction methodologies have a clear impact on the estimated growth traits, emphasising the need for proper standardization in data analysis. PRECOG is a tool that streamlines growth data pre-processing, phenotypic trait extraction, visualization, distribution and the creation of vast and informative phenomics databases.

A phenome database (NEAUHLFPD) designed and constructed for broiler lines divergently selected for abdominal fat content.

PubMed

Li, Min; Dong, Xiang-yu; Liang, Hao; Leng, Li; Zhang, Hui; Wang, Shou-zhi; Li, Hui; Du, Zhi-Qiang

2017-05-20

Effective management and analysis of precisely recorded phenotypic traits are important components of the selection and breeding of superior livestocks. Over two decades, we divergently selected chicken lines for abdominal fat content at Northeast Agricultural University (Northeast Agricultural University High and Low Fat, NEAUHLF), and collected large volume of phenotypic data related to the investigation on molecular genetic basis of adipose tissue deposition in broilers. To effectively and systematically store, manage and analyze phenotypic data, we built the NEAUHLF Phenome Database (NEAUHLFPD). NEAUHLFPD included the following phenotypic records: pedigree (generations 1-19) and 29 phenotypes, such as body sizes and weights, carcass traits and their corresponding rates. The design and construction strategy of NEAUHLFPD were executed as follows: (1) Framework design. We used Apache as our web server, MySQL and Navicat as database management tools, and PHP as the HTML-embedded language to create dynamic interactive website. (2) Structural components. On the main interface, detailed introduction on the composition, function, and the index buttons of the basic structure of the database could be found. The functional modules of NEAUHLFPD had two main components: the first module referred to the physical storage space for phenotypic data, in which functional manipulation on data can be realized, such as data indexing, filtering, range-setting, searching, etc.; the second module related to the calculation of basic descriptive statistics, where data filtered from the database can be used for the computation of basic statistical parameters and the simultaneous conditional sorting. NEAUHLFPD could be used to effectively store and manage not only phenotypic, but also genotypic and genomics data, which can facilitate further investigation on the molecular genetic basis of chicken adipose tissue growth and development, and expedite the selection and breeding of broilers with low fat content.

Genomic, transcriptomic and phenomic variation reveals the complex adaptation to stress response of modern maize breeding

USDA-ARS?s Scientific Manuscript database

Early maize adaptation to different agricultural environments was an important process associated with the creation of a stable food supply that allowed the evolution of human civilization in the Americas. To explore the mechanisms of maize adaptation, genomic, transcriptomic and phenomic data were ...

Phage phenomics: Physiological approaches to characterize novel viral proteins

ScienceCinema

Sanchez, Savannah E. [San Diego State Univ., San Diego, CA (United States); Cuevas, Daniel A. [San Diego State Univ., San Diego, CA (United States); Rostron, Jason E. [San Diego State Univ., San Diego, CA (United States); Liang, Tiffany Y. [San Diego State Univ., San Diego, CA (United States); Pivaroff, Cullen G. [San Diego State Univ., San Diego, CA (United States); Haynes, Matthew R. [San Diego State Univ., San Diego, CA (United States); Nulton, Jim [San Diego State Univ., San Diego, CA (United States); Felts, Ben [San Diego State Univ., San Diego, CA (United States); Bailey, Barbara A. [San Diego State Univ., San Diego, CA (United States); Salamon, Peter [San Diego State Univ., San Diego, CA (United States); Edwards, Robert A. [San Diego State Univ., San Diego, CA (United States); Argonne National Lab. (ANL), Argonne, IL (United States); Burgin, Alex B. [Broad Institute, Cambridge, MA (United States); Segall, Anca M. [San Diego State Univ., San Diego, CA (United States); Rohwer, Forest [San Diego State Univ., San Diego, CA (United States)

2018-06-21

Current investigations into phage-host interactions are dependent on extrapolating knowledge from (meta)genomes. Interestingly, 60 - 95% of all phage sequences share no homology to current annotated proteins. As a result, a large proportion of phage genes are annotated as hypothetical. This reality heavily affects the annotation of both structural and auxiliary metabolic genes. Here we present phenomic methods designed to capture the physiological response(s) of a selected host during expression of one of these unknown phage genes. Multi-phenotype Assay Plates (MAPs) are used to monitor the diversity of host substrate utilization and subsequent biomass formation, while metabolomics provides bi-product analysis by monitoring metabolite abundance and diversity. Both tools are used simultaneously to provide a phenotypic profile associated with expression of a single putative phage open reading frame (ORF). Thus, representative results for both methods are compared, highlighting the phenotypic profile differences of a host carrying either putative structural or metabolic phage genes. In addition, the visualization techniques and high throughput computational pipelines that facilitated experimental analysis are presented.

Machine Learning and Computer Vision System for Phenotype Data Acquisition and Analysis in Plants.

PubMed

Navarro, Pedro J; Pérez, Fernando; Weiss, Julia; Egea-Cortines, Marcos

2016-05-05

Phenomics is a technology-driven approach with promising future to obtain unbiased data of biological systems. Image acquisition is relatively simple. However data handling and analysis are not as developed compared to the sampling capacities. We present a system based on machine learning (ML) algorithms and computer vision intended to solve the automatic phenotype data analysis in plant material. We developed a growth-chamber able to accommodate species of various sizes. Night image acquisition requires near infrared lightning. For the ML process, we tested three different algorithms: k-nearest neighbour (kNN), Naive Bayes Classifier (NBC), and Support Vector Machine. Each ML algorithm was executed with different kernel functions and they were trained with raw data and two types of data normalisation. Different metrics were computed to determine the optimal configuration of the machine learning algorithms. We obtained a performance of 99.31% in kNN for RGB images and a 99.34% in SVM for NIR. Our results show that ML techniques can speed up phenomic data analysis. Furthermore, both RGB and NIR images can be segmented successfully but may require different ML algorithms for segmentation.

TERRA REF: Advancing phenomics with high resolution, open access sensor and genomics data

NASA Astrophysics Data System (ADS)

LeBauer, D.; Kooper, R.; Burnette, M.; Willis, C.

2017-12-01

Automated plant measurement has the potential to improve understanding of genetic and environmental controls on plant traits (phenotypes). The application of sensors and software in the automation of high throughput phenotyping reflects a fundamental shift from labor intensive hand measurements to drone, tractor, and robot mounted sensing platforms. These tools are expected to speed the rate of crop improvement by enabling plant breeders to more accurately select plants with improved yields, resource use efficiency, and stress tolerance. However, there are many challenges facing high throughput phenomics: sensors and platforms are expensive, currently there are few standard methods of data collection and storage, and the analysis of large data sets requires high performance computers and automated, reproducible computing pipelines. To overcome these obstacles and advance the science of high throughput phenomics, the TERRA Phenotyping Reference Platform (TERRA-REF) team is developing an open-access database of high resolution sensor data. TERRA REF is an integrated field and greenhouse phenotyping system that includes: a reference field scanner with fifteen sensors that can generate terrabytes of data each day at mm resolution; UAV, tractor, and fixed field sensing platforms; and an automated controlled-environment scanner. These platforms will enable investigation of diverse sensing modalities, and the investigation of traits under controlled and field environments. It is the goal of TERRA REF to lower the barrier to entry for academic and industry researchers by providing high-resolution data, open source software, and online computing resources. Our project is unique in that all data will be made fully public in November 2018, and is already available to early adopters through the beta-user program. We will describe the datasets and how to use them as well as the databases and computing pipeline and how these can be reused and remixed in other phenomics pipelines. Finally, we will describe the National Data Service workbench, a cloud computing platform that can access the petabyte scale data while supporting reproducible research.

Targeting the untargeted in molecular phenomics with structurally-selective ion mobility-mass spectrometry.

PubMed

May, Jody Christopher; Gant-Branum, Randi Lee; McLean, John Allen

2016-06-01

Systems-wide molecular phenomics is rapidly expanding through technological advances in instrumentation and bioinformatics. Strategies such as structural mass spectrometry, which utilizes size and shape measurements with molecular weight, serve to characterize the sum of molecular expression in biological contexts, where broad-scale measurements are made that are interpreted through big data statistical techniques to reveal underlying patterns corresponding to phenotype. The data density, data dimensionality, data projection, and data interrogation are all critical aspects of these approaches to turn data into salient information. Untargeted molecular phenomics is already having a dramatic impact in discovery science from drug discovery to synthetic biology. It is evident that these emerging techniques will integrate closely in broad efforts aimed at precision medicine. Copyright © 2016 Elsevier Ltd. All rights reserved.

The plant ontology as a tool for comparative plant anatomy and genomic analyses

USDA-ARS?s Scientific Manuscript database

Plant science is now a major player in the fields of genomics, gene expression analysis, phenomics and metabolomics. Recent advances in sequencing technologies have led to a windfall of data, with new species being added rapidly to the list of species whose genomes have been decoded. The Plant Ontol...

Automated 3D Phenotype Analysis Using Data Mining

PubMed Central

Plyusnin, Ilya; Evans, Alistair R.; Karme, Aleksis; Gionis, Aristides; Jernvall, Jukka

2008-01-01

The ability to analyze and classify three-dimensional (3D) biological morphology has lagged behind the analysis of other biological data types such as gene sequences. Here, we introduce the techniques of data mining to the study of 3D biological shapes to bring the analyses of phenomes closer to the efficiency of studying genomes. We compiled five training sets of highly variable morphologies of mammalian teeth from the MorphoBrowser database. Samples were labeled either by dietary class or by conventional dental types (e.g. carnassial, selenodont). We automatically extracted a multitude of topological attributes using Geographic Information Systems (GIS)-like procedures that were then used in several combinations of feature selection schemes and probabilistic classification models to build and optimize classifiers for predicting the labels of the training sets. In terms of classification accuracy, computational time and size of the feature sets used, non-repeated best-first search combined with 1-nearest neighbor classifier was the best approach. However, several other classification models combined with the same searching scheme proved practical. The current study represents a first step in the automatic analysis of 3D phenotypes, which will be increasingly valuable with the future increase in 3D morphology and phenomics databases. PMID:18320060

Genomic and Phenomic Study of Mammary Pathogenic Escherichia coli

PubMed Central

Blum, Shlomo E.; Heller, Elimelech D.; Sela, Shlomo; Elad, Daniel; Edery, Nir; Leitner, Gabriel

2015-01-01

Escherichia coli is a major etiological agent of intra-mammary infections (IMI) in cows, leading to acute mastitis and causing great economic losses in dairy production worldwide. Particular strains cause persistent IMI, leading to recurrent mastitis. Virulence factors of mammary pathogenic E. coli (MPEC) involved pathogenesis of mastitis as well as those differentiating strains causing acute or persistent mastitis are largely unknown. This study aimed to identify virulence markers in MPEC through whole genome and phenome comparative analysis. MPEC strains causing acute (VL2874 and P4) or persistent (VL2732) mastitis were compared to an environmental strain (K71) and to the genomes of strains representing different E. coli pathotypes. Intra-mammary challenge in mice confirmed experimentally that the strains studied here have different pathogenic potential, and that the environmental strain K71 is non-pathogenic in the mammary gland. Analysis of whole genome sequences and predicted proteomes revealed high similarity among MPEC, whereas MPEC significantly differed from the non-mammary pathogenic strain K71, and from E. coli genomes from other pathotypes. Functional features identified in MPEC genomes and lacking in the non-mammary pathogenic strain were associated with synthesis of lipopolysaccharide and other membrane antigens, ferric-dicitrate iron acquisition and sugars metabolism. Features associated with cytotoxicity or intra-cellular survival were found specifically in the genomes of strains from severe and acute (VL2874) or persistent (VL2732) mastitis, respectively. MPEC genomes were relatively similar to strain K-12, which was subsequently shown here to be possibly pathogenic in the mammary gland. Phenome analysis showed that the persistent MPEC was the most versatile in terms of nutrients metabolized and acute MPEC the least. Among phenotypes unique to MPEC compared to the non-mammary pathogenic strain were uric acid and D-serine metabolism. This study reveals virulence factors and phenotypic characteristics of MPEC that may play a role in pathogenesis of E. coli mastitis. PMID:26327312

Latin America: A Development Pole for Phenomics

PubMed Central

Camargo, Anyela V.; Lobos, Gustavo A.

2016-01-01

Latin America and the Caribbean (LAC) has long been associated with the production and export of a diverse range of agricultural commodities. Due to its strategic geographic location, which encompasses a wide range of climates, it is possible to produce almost any crop. The climate diversity in LAC is a major factor in its agricultural potential but this also means climate change represents a real threat to the region. Therefore, LAC farming must prepare and quickly adapt to an environment that is likely to feature long periods of drought, excessive rainfall and extreme temperatures. With the aim of moving toward a more resilient agriculture, LAC scientists have created the Latin American Plant Phenomics Network (LatPPN) which focuses on LAC's economically important crops. LatPPN's key strategies to achieve its main goal are: (1) training of LAC members on plant phenomics and phenotyping, (2) establish international and multidisciplinary collaborations, (3) develop standards for data exchange and research protocols, (4) share equipment and infrastructure, (5) disseminate data and research results, (6) identify funding opportunities and (7) develop strategies to guarantee LatPPN's relevance and sustainability across time. Despite the challenges ahead, LatPPN represents a big step forward toward the consolidation of a common mind-set in the field of plant phenotyping and phenomics in LAC. PMID:27999577

Latin America: A Development Pole for Phenomics.

PubMed

Camargo, Anyela V; Lobos, Gustavo A

2016-01-01

Latin America and the Caribbean (LAC) has long been associated with the production and export of a diverse range of agricultural commodities. Due to its strategic geographic location, which encompasses a wide range of climates, it is possible to produce almost any crop. The climate diversity in LAC is a major factor in its agricultural potential but this also means climate change represents a real threat to the region. Therefore, LAC farming must prepare and quickly adapt to an environment that is likely to feature long periods of drought, excessive rainfall and extreme temperatures. With the aim of moving toward a more resilient agriculture, LAC scientists have created the Latin American Plant Phenomics Network (LatPPN) which focuses on LAC's economically important crops. LatPPN's key strategies to achieve its main goal are: (1) training of LAC members on plant phenomics and phenotyping, (2) establish international and multidisciplinary collaborations, (3) develop standards for data exchange and research protocols, (4) share equipment and infrastructure, (5) disseminate data and research results, (6) identify funding opportunities and (7) develop strategies to guarantee LatPPN's relevance and sustainability across time. Despite the challenges ahead, LatPPN represents a big step forward toward the consolidation of a common mind-set in the field of plant phenotyping and phenomics in LAC.

Preprocessed Consortium for Neuropsychiatric Phenomics dataset.

PubMed

Gorgolewski, Krzysztof J; Durnez, Joke; Poldrack, Russell A

2017-01-01

Here we present preprocessed MRI data of 265 participants from the Consortium for Neuropsychiatric Phenomics (CNP) dataset. The preprocessed dataset includes minimally preprocessed data in the native, MNI and surface spaces accompanied with potential confound regressors, tissue probability masks, brain masks and transformations. In addition the preprocessed dataset includes unthresholded group level and single subject statistical maps from all tasks included in the original dataset. We hope that availability of this dataset will greatly accelerate research.

Zebrafish neurobehavioral phenomics for aquatic neuropharmacology and toxicology research.

PubMed

Kalueff, Allan V; Echevarria, David J; Homechaudhuri, Sumit; Stewart, Adam Michael; Collier, Adam D; Kaluyeva, Aleksandra A; Li, Shaomin; Liu, Yingcong; Chen, Peirong; Wang, JiaJia; Yang, Lei; Mitra, Anisa; Pal, Subharthi; Chaudhuri, Adwitiya; Roy, Anwesha; Biswas, Missidona; Roy, Dola; Podder, Anupam; Poudel, Manoj K; Katare, Deepshikha P; Mani, Ruchi J; Kyzar, Evan J; Gaikwad, Siddharth; Nguyen, Michael; Song, Cai

2016-01-01

Zebrafish (Danio rerio) are rapidly emerging as an important model organism for aquatic neuropharmacology and toxicology research. The behavioral/phenotypic complexity of zebrafish allows for thorough dissection of complex human brain disorders and drug-evoked pathological states. As numerous zebrafish models become available with a wide spectrum of behavioral, genetic, and environmental methods to test novel drugs, here we discuss recent zebrafish phenomics methods to facilitate drug discovery, particularly in the field of biological psychiatry. Additionally, behavioral, neurological, and endocrine endpoints are becoming increasingly well-characterized in zebrafish, making them an inexpensive, robust and effective model for toxicology research and pharmacological screening. We also discuss zebrafish behavioral phenotypes, experimental considerations, pharmacological candidates and relevance of zebrafish neurophenomics to other 'omics' (e.g., genomic, proteomic) approaches. Finally, we critically evaluate the limitations of utilizing this model organism, and outline future strategies of research in the field of zebrafish phenomics. Copyright © 2015 Elsevier B.V. All rights reserved.

The genome and phenome of the green alga Chloroidium sp. UTEX 3007 reveal adaptive traits for desert acclimatization.

PubMed

Nelson, David R; Khraiwesh, Basel; Fu, Weiqi; Alseekh, Saleh; Jaiswal, Ashish; Chaiboonchoe, Amphun; Hazzouri, Khaled M; O'Connor, Matthew J; Butterfoss, Glenn L; Drou, Nizar; Rowe, Jillian D; Harb, Jamil; Fernie, Alisdair R; Gunsalus, Kristin C; Salehi-Ashtiani, Kourosh

2017-06-17

To investigate the phenomic and genomic traits that allow green algae to survive in deserts, we characterized a ubiquitous species, Chloroidium sp. UTEX 3007 , which we isolated from multiple locations in the United Arab Emirates (UAE). Metabolomic analyses of Chloroidium sp. UTEX 3007 indicated that the alga accumulates a broad range of carbon sources, including several desiccation tolerance-promoting sugars and unusually large stores of palmitate. Growth assays revealed capacities to grow in salinities from zero to 60 g/L and to grow heterotrophically on >40 distinct carbon sources. Assembly and annotation of genomic reads yielded a 52.5 Mbp genome with 8153 functionally annotated genes. Comparison with other sequenced green algae revealed unique protein families involved in osmotic stress tolerance and saccharide metabolism that support phenomic studies. Our results reveal the robust and flexible biology utilized by a green alga to successfully inhabit a desert coastline.

Towards an Age-Phenome Knowledge-base

PubMed Central

2011-01-01

Background Currently, data about age-phenotype associations are not systematically organized and cannot be studied methodically. Searching for scientific articles describing phenotypic changes reported as occurring at a given age is not possible for most ages. Results Here we present the Age-Phenome Knowledge-base (APK), in which knowledge about age-related phenotypic patterns and events can be modeled and stored for retrieval. The APK contains evidence connecting specific ages or age groups with phenotypes, such as disease and clinical traits. Using a simple text mining tool developed for this purpose, we extracted instances of age-phenotype associations from journal abstracts related to non-insulin-dependent Diabetes Mellitus. In addition, links between age and phenotype were extracted from clinical data obtained from the NHANES III survey. The knowledge stored in the APK is made available for the relevant research community in the form of 'Age-Cards', each card holds the collection of all the information stored in the APK about a particular age. These Age-Cards are presented in a wiki, allowing community review, amendment and contribution of additional information. In addition to the wiki interaction, complex searches can also be conducted which require the user to have some knowledge of database query construction. Conclusions The combination of a knowledge model based repository with community participation in the evolution and refinement of the knowledge-base makes the APK a useful and valuable environment for collecting and curating existing knowledge of the connections between age and phenotypes. PMID:21651792

Open reading frames associated with cancer in the dark matter of the human genome.

PubMed

Delgado, Ana Paula; Brandao, Pamela; Chapado, Maria Julia; Hamid, Sheilin; Narayanan, Ramaswamy

2014-01-01

The uncharacterized proteins (open reading frames, ORFs) in the human genome offer an opportunity to discover novel targets for cancer. A systematic analysis of the dark matter of the human proteome for druggability and biomarker discovery is crucial to mining the genome. Numerous data mining tools are available to mine these ORFs to develop a comprehensive knowledge base for future target discovery and validation. Using the Genetic Association Database, the ORFs of the human dark matter proteome were screened for evidence of association with neoplasms. The Phenome-Genome Integrator tool was used to establish phenotypic association with disease traits including cancer. Batch analysis of the tools for protein expression analysis, gene ontology and motifs and domains was used to characterize the ORFs. Sixty-two ORFs were identified for neoplasm association. The expression Quantitative Trait Loci (eQTL) analysis identified thirteen ORFs related to cancer traits. Protein expression, motifs and domain analysis and genome-wide association studies verified the relevance of these OncoORFs in diverse tumors. The OncoORFs are also associated with a wide variety of human diseases and disorders. Our results link the OncoORFs to diverse diseases and disorders. This suggests a complex landscape of the uncharacterized proteome in human diseases. These results open the dark matter of the proteome to novel cancer target research. Copyright© 2014, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

Clinical lipidomics: a new way to diagnose human diseases.

PubMed

Lv, Jiapei; Zhang, Linlin; Yan, Furong; Wang, Xiangdong

2018-04-27

Lipidomics is a measurement of a large scale of lipid species to understand roles of their carbon atoms, dual bonds, or isomerism in the lipid molecule. Clinical lipidomics was recently defined "as a new integrative biomedicine to discover the correlation and regulation between a large scale of lipid elements measured and analyzed in liquid biopsies from patients with those patient phenomes and clinical phenotypes". The first step to translate lipidomics into clinical lipidomics is to settle a number of standard operation procedures and protocols of lipidomics performance and measurement. Clinical lipidomics is the part of clinical trans-omics which was coined as a new emerging scientific discipline where clinical phenomes are integrated with molecular multiomics. We believe it is the time to translate lipid science and lipidomics into clinical application and to understand the importance of clinical lipidomics as one of the most helpful approaches during the design and decision-making of therapeutic strategies for individuals. We emphasize here that clinical lipidomics should be merged with clinical phenomes, e.g. patient signs and symptoms, biomedical analyses, pathology, images, and responses to therapies, although it is difficult to integrate and fuse the information of clinical lipidomics with clinical phenomes. It will be a great achievement if we can draw the networks of lipidomic species fused with networks of genes and proteins to describe the molecular mechanisms of the disease in multi-dimensions.

The genome and phenome of the green alga Chloroidium sp. UTEX 3007 reveal adaptive traits for desert acclimatization

PubMed Central

Nelson, David R; Khraiwesh, Basel; Fu, Weiqi; Alseekh, Saleh; Jaiswal, Ashish; Chaiboonchoe, Amphun; Hazzouri, Khaled M; O’Connor, Matthew J; Butterfoss, Glenn L; Drou, Nizar; Rowe, Jillian D; Harb, Jamil; Fernie, Alisdair R; Gunsalus, Kristin C; Salehi-Ashtiani, Kourosh

2017-01-01

To investigate the phenomic and genomic traits that allow green algae to survive in deserts, we characterized a ubiquitous species, Chloroidium sp. UTEX 3007, which we isolated from multiple locations in the United Arab Emirates (UAE). Metabolomic analyses of Chloroidium sp. UTEX 3007 indicated that the alga accumulates a broad range of carbon sources, including several desiccation tolerance-promoting sugars and unusually large stores of palmitate. Growth assays revealed capacities to grow in salinities from zero to 60 g/L and to grow heterotrophically on >40 distinct carbon sources. Assembly and annotation of genomic reads yielded a 52.5 Mbp genome with 8153 functionally annotated genes. Comparison with other sequenced green algae revealed unique protein families involved in osmotic stress tolerance and saccharide metabolism that support phenomic studies. Our results reveal the robust and flexible biology utilized by a green alga to successfully inhabit a desert coastline. DOI: http://dx.doi.org/10.7554/eLife.25783.001 PMID:28623667

Cancer Imaging Phenomics Toolkit (CaPTk) | Informatics Technology for Cancer Research (ITCR)

Cancer.gov

CaPTk is a software toolkit to facilitate translation of quantitative image analysis methods that help us obtain rich imaging phenotypic signatures of oncologic images and relate them to precision diagnostics and prediction of clinical outcomes, as well as to underlying molecular characteristics of cancer. The stand-alone graphical user interface of CaPTk brings analysis methods from the realm of medical imaging research to the clinic, and will be extended to use web-based services for computationally-demanding pipelines.

World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project: I. Surgical phenotype data collection in endometriosis research

PubMed Central

Becker, Christian M.; Laufer, Marc R.; Stratton, Pamela; Hummelshoj, Lone; Missmer, Stacey A.; Zondervan, Krina T.; Adamson, G. David; Adamson, G.D.; Allaire, C.; Anchan, R.; Becker, C.M.; Bedaiwy, M.A.; Buck Louis, G.M.; Calhaz-Jorge, C.; Chwalisz, K.; D'Hooghe, T.M.; Fassbender, A.; Faustmann, T.; Fazleabas, A.T.; Flores, I.; Forman, A.; Fraser, I.; Giudice, L.C.; Gotte, M.; Gregersen, P.; Guo, S.-W.; Harada, T.; Hartwell, D.; Horne, A.W.; Hull, M.L.; Hummelshoj, L.; Ibrahim, M.G.; Kiesel, L.; Laufer, M.R.; Machens, K.; Mechsner, S.; Missmer, S.A.; Montgomery, G.W.; Nap, A.; Nyegaard, M.; Osteen, K.G.; Petta, C.A.; Rahmioglu, N.; Renner, S.P.; Riedlinger, J.; Roehrich, S.; Rogers, P.A.; Rombauts, L.; Salumets, A.; Saridogan, E.; Seckin, T.; Stratton, P.; Sharpe-Timms, K.L.; Tworoger, S.; Vigano, P.; Vincent, K.; Vitonis, A.F.; Wienhues-Thelen, U.-H.; Yeung, P.P.; Yong, P.; Zondervan, K.T.

2014-01-01

Objective To standardize the recording of surgical phenotypic information on endometriosis and related sample collections obtained at laparoscopy, allowing large-scale collaborative research into the condition. Design An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries. Setting Two workshops were conducted in 2013, bringing together 54 clinical, academic, and industry leaders in endometriosis research and management worldwide. Patient(s) None. Intervention(s) A postsurgical scoring sheet containing general and gynecological patient and procedural information, extent of disease, the location and type of endometriotic lesion, and any other findings was developed during several rounds of review. Comments and any systematic surgical data collection tools used in the reviewers' centers were incorporated. Main Outcome Measure(s) The development of a standard recommended (SSF) and minimum required (MSF) form to collect data on the surgical phenotype of endometriosis. Result(s) SSF and MSF include detailed descriptions of lesions, modes of procedures and sample collection, comorbidities, and potential residual disease at the end of surgery, along with previously published instruments such as the revised American Society for Reproductive Medicine and Endometriosis Fertility Index classification tools for comparison and validation. Conclusion(s) This is the first multicenter, international collaboration between academic centers and industry addressing standardization of phenotypic data collection for a specific disease. The Endometriosis Phenome and Biobanking Harmonisation Project SSF and MSF are essential tools to increase our understanding of the pathogenesis of endometriosis by allowing large-scale collaborative research into the condition. PMID:25150390

Phage phenomics: Physiological approaches to characterize novel viral proteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanchez, Savannah E.; Cuevas, Daniel A.; Rostron, Jason E.

Current investigations into phage-host interactions are dependent on extrapolating knowledge from (meta)genomes. Interestingly, 60 - 95% of all phage sequences share no homology to current annotated proteins. As a result, a large proportion of phage genes are annotated as hypothetical. This reality heavily affects the annotation of both structural and auxiliary metabolic genes. Here we present phenomic methods designed to capture the physiological response(s) of a selected host during expression of one of these unknown phage genes. Multi-phenotype Assay Plates (MAPs) are used to monitor the diversity of host substrate utilization and subsequent biomass formation, while metabolomics provides bi-product analysismore » by monitoring metabolite abundance and diversity. Both tools are used simultaneously to provide a phenotypic profile associated with expression of a single putative phage open reading frame (ORF). Thus, representative results for both methods are compared, highlighting the phenotypic profile differences of a host carrying either putative structural or metabolic phage genes. In addition, the visualization techniques and high throughput computational pipelines that facilitated experimental analysis are presented.« less

Familial aggregation of focal seizure semiology in the Epilepsy Phenome/Genome Project.

PubMed

Tobochnik, Steven; Fahlstrom, Robyn; Shain, Catherine; Winawer, Melodie R

2017-07-04

To improve phenotype definition in genetic studies of epilepsy, we assessed the familial aggregation of focal seizure types and of specific seizure symptoms within the focal epilepsies in families from the Epilepsy Phenome/Genome Project. We studied 302 individuals with nonacquired focal epilepsy from 149 families. Familial aggregation was assessed by logistic regression analysis of relatives' traits (dependent variable) by probands' traits (independent variable), estimating the odds ratio for each symptom in a relative given presence vs absence of the symptom in the proband. In families containing multiple individuals with nonacquired focal epilepsy, we found significant evidence for familial aggregation of ictal motor, autonomic, psychic, and aphasic symptoms. Within these categories, ictal whole body posturing, diaphoresis, dyspnea, fear/anxiety, and déjà vu/jamais vu showed significant familial aggregation. Focal seizure type aggregated as well, including complex partial, simple partial, and secondarily generalized tonic-clonic seizures. Our results provide insight into genotype-phenotype correlation in the nonacquired focal epilepsies and a framework for identifying subgroups of patients likely to share susceptibility genes. © 2017 American Academy of Neurology.

Phage phenomics: Physiological approaches to characterize novel viral proteins

DOE PAGES

Sanchez, Savannah E.; Cuevas, Daniel A.; Rostron, Jason E.; ...

2015-06-11

Current investigations into phage-host interactions are dependent on extrapolating knowledge from (meta)genomes. Interestingly, 60 - 95% of all phage sequences share no homology to current annotated proteins. As a result, a large proportion of phage genes are annotated as hypothetical. This reality heavily affects the annotation of both structural and auxiliary metabolic genes. Here we present phenomic methods designed to capture the physiological response(s) of a selected host during expression of one of these unknown phage genes. Multi-phenotype Assay Plates (MAPs) are used to monitor the diversity of host substrate utilization and subsequent biomass formation, while metabolomics provides bi-product analysismore » by monitoring metabolite abundance and diversity. Both tools are used simultaneously to provide a phenotypic profile associated with expression of a single putative phage open reading frame (ORF). Thus, representative results for both methods are compared, highlighting the phenotypic profile differences of a host carrying either putative structural or metabolic phage genes. In addition, the visualization techniques and high throughput computational pipelines that facilitated experimental analysis are presented.« less

Cancer imaging phenomics toolkit: quantitative imaging analytics for precision diagnostics and predictive modeling of clinical outcome.

PubMed

Davatzikos, Christos; Rathore, Saima; Bakas, Spyridon; Pati, Sarthak; Bergman, Mark; Kalarot, Ratheesh; Sridharan, Patmaa; Gastounioti, Aimilia; Jahani, Nariman; Cohen, Eric; Akbari, Hamed; Tunc, Birkan; Doshi, Jimit; Parker, Drew; Hsieh, Michael; Sotiras, Aristeidis; Li, Hongming; Ou, Yangming; Doot, Robert K; Bilello, Michel; Fan, Yong; Shinohara, Russell T; Yushkevich, Paul; Verma, Ragini; Kontos, Despina

2018-01-01

The growth of multiparametric imaging protocols has paved the way for quantitative imaging phenotypes that predict treatment response and clinical outcome, reflect underlying cancer molecular characteristics and spatiotemporal heterogeneity, and can guide personalized treatment planning. This growth has underlined the need for efficient quantitative analytics to derive high-dimensional imaging signatures of diagnostic and predictive value in this emerging era of integrated precision diagnostics. This paper presents cancer imaging phenomics toolkit (CaPTk), a new and dynamically growing software platform for analysis of radiographic images of cancer, currently focusing on brain, breast, and lung cancer. CaPTk leverages the value of quantitative imaging analytics along with machine learning to derive phenotypic imaging signatures, based on two-level functionality. First, image analysis algorithms are used to extract comprehensive panels of diverse and complementary features, such as multiparametric intensity histogram distributions, texture, shape, kinetics, connectomics, and spatial patterns. At the second level, these quantitative imaging signatures are fed into multivariate machine learning models to produce diagnostic, prognostic, and predictive biomarkers. Results from clinical studies in three areas are shown: (i) computational neuro-oncology of brain gliomas for precision diagnostics, prediction of outcome, and treatment planning; (ii) prediction of treatment response for breast and lung cancer, and (iii) risk assessment for breast cancer.

First Higher-Multipole Model of Gravitational Waves from Spinning and Coalescing Black-Hole Binaries

NASA Astrophysics Data System (ADS)

London, Lionel; Khan, Sebastian; Fauchon-Jones, Edward; García, Cecilio; Hannam, Mark; Husa, Sascha; Jiménez-Forteza, Xisco; Kalaghatgi, Chinmay; Ohme, Frank; Pannarale, Francesco

2018-04-01

Gravitational-wave observations of binary black holes currently rely on theoretical models that predict the dominant multipoles (ℓ=2 ,|m |=2 ) of the radiation during inspiral, merger, and ringdown. We introduce a simple method to include the subdominant multipoles to binary black hole gravitational waveforms, given a frequency-domain model for the dominant multipoles. The amplitude and phase of the original model are appropriately stretched and rescaled using post-Newtonian results (for the inspiral), perturbation theory (for the ringdown), and a smooth transition between the two. No additional tuning to numerical-relativity simulations is required. We apply a variant of this method to the nonprecessing PhenomD model. The result, PhenomHM, constitutes the first higher-multipole model of spinning and coalescing black-hole binaries, and currently includes the (ℓ,|m |)=(2 ,2 ),(3 ,3 ),(4 ,4 ),(2 ,1 ),(3 ,2 ),(4 ,3 ) radiative moments. Comparisons with numerical-relativity waveforms demonstrate that PhenomHM is more accurate than dominant-multipole-only models for all binary configurations, and typically improves the measurement of binary properties.

First Higher-Multipole Model of Gravitational Waves from Spinning and Coalescing Black-Hole Binaries.

PubMed

London, Lionel; Khan, Sebastian; Fauchon-Jones, Edward; García, Cecilio; Hannam, Mark; Husa, Sascha; Jiménez-Forteza, Xisco; Kalaghatgi, Chinmay; Ohme, Frank; Pannarale, Francesco

2018-04-20

Gravitational-wave observations of binary black holes currently rely on theoretical models that predict the dominant multipoles (ℓ=2,|m|=2) of the radiation during inspiral, merger, and ringdown. We introduce a simple method to include the subdominant multipoles to binary black hole gravitational waveforms, given a frequency-domain model for the dominant multipoles. The amplitude and phase of the original model are appropriately stretched and rescaled using post-Newtonian results (for the inspiral), perturbation theory (for the ringdown), and a smooth transition between the two. No additional tuning to numerical-relativity simulations is required. We apply a variant of this method to the nonprecessing PhenomD model. The result, PhenomHM, constitutes the first higher-multipole model of spinning and coalescing black-hole binaries, and currently includes the (ℓ,|m|)=(2,2),(3,3),(4,4),(2,1),(3,2),(4,3) radiative moments. Comparisons with numerical-relativity waveforms demonstrate that PhenomHM is more accurate than dominant-multipole-only models for all binary configurations, and typically improves the measurement of binary properties.

A phenome-wide examination of neural and cognitive function.

PubMed

Poldrack, R A; Congdon, E; Triplett, W; Gorgolewski, K J; Karlsgodt, K H; Mumford, J A; Sabb, F W; Freimer, N B; London, E D; Cannon, T D; Bilder, R M

2016-12-06

This data descriptor outlines a shared neuroimaging dataset from the UCLA Consortium for Neuropsychiatric Phenomics, which focused on understanding the dimensional structure of memory and cognitive control (response inhibition) functions in both healthy individuals (130 subjects) and individuals with neuropsychiatric disorders including schizophrenia (50 subjects), bipolar disorder (49 subjects), and attention deficit/hyperactivity disorder (43 subjects). The dataset includes an extensive set of task-based fMRI assessments, resting fMRI, structural MRI, and high angular resolution diffusion MRI. The dataset is shared through the OpenfMRI project, and is formatted according to the Brain Imaging Data Structure (BIDS) standard.

Remote Sensing and Reflectance Profiling in Entomology.

PubMed

Nansen, Christian; Elliott, Norman

2016-01-01

Remote sensing describes the characterization of the status of objects and/or the classification of their identity based on a combination of spectral features extracted from reflectance or transmission profiles of radiometric energy. Remote sensing can be benchtop based, and therefore acquired at a high spatial resolution, or airborne at lower spatial resolution to cover large areas. Despite important challenges, airborne remote sensing technologies will undoubtedly be of major importance in optimized management of agricultural systems in the twenty-first century. Benchtop remote sensing applications are becoming important in insect systematics and in phenomics studies of insect behavior and physiology. This review highlights how remote sensing influences entomological research by enabling scientists to nondestructively monitor how individual insects respond to treatments and ambient conditions. Furthermore, novel remote sensing technologies are creating intriguing interdisciplinary bridges between entomology and disciplines such as informatics and electrical engineering.

Microbial phenomics information extractor (MicroPIE): a natural language processing tool for the automated acquisition of prokaryotic phenotypic characters from text sources.

PubMed

Mao, Jin; Moore, Lisa R; Blank, Carrine E; Wu, Elvis Hsin-Hui; Ackerman, Marcia; Ranade, Sonali; Cui, Hong

2016-12-13

The large-scale analysis of phenomic data (i.e., full phenotypic traits of an organism, such as shape, metabolic substrates, and growth conditions) in microbial bioinformatics has been hampered by the lack of tools to rapidly and accurately extract phenotypic data from existing legacy text in the field of microbiology. To quickly obtain knowledge on the distribution and evolution of microbial traits, an information extraction system needed to be developed to extract phenotypic characters from large numbers of taxonomic descriptions so they can be used as input to existing phylogenetic analysis software packages. We report the development and evaluation of Microbial Phenomics Information Extractor (MicroPIE, version 0.1.0). MicroPIE is a natural language processing application that uses a robust supervised classification algorithm (Support Vector Machine) to identify characters from sentences in prokaryotic taxonomic descriptions, followed by a combination of algorithms applying linguistic rules with groups of known terms to extract characters as well as character states. The input to MicroPIE is a set of taxonomic descriptions (clean text). The output is a taxon-by-character matrix-with taxa in the rows and a set of 42 pre-defined characters (e.g., optimum growth temperature) in the columns. The performance of MicroPIE was evaluated against a gold standard matrix and another student-made matrix. Results show that, compared to the gold standard, MicroPIE extracted 21 characters (50%) with a Relaxed F1 score > 0.80 and 16 characters (38%) with Relaxed F1 scores ranging between 0.50 and 0.80. Inclusion of a character prediction component (SVM) improved the overall performance of MicroPIE, notably the precision. Evaluated against the same gold standard, MicroPIE performed significantly better than the undergraduate students. MicroPIE is a promising new tool for the rapid and efficient extraction of phenotypic character information from prokaryotic taxonomic descriptions. However, further development, including incorporation of ontologies, will be necessary to improve the performance of the extraction for some character types.

Integration of multi-omics techniques and physiological phenotyping within a holistic phenomics approach to study senescence in model and crop plants.

PubMed

Großkinsky, Dominik K; Syaifullah, Syahnada Jaya; Roitsch, Thomas

2018-02-12

The study of senescence in plants is complicated by diverse levels of temporal and spatial dynamics as well as the impact of external biotic and abiotic factors and crop plant management. Whereas the molecular mechanisms involved in developmentally regulated leaf senescence are very well understood, in particular in the annual model plant species Arabidopsis, senescence of other organs such as the flower, fruit, and root is much less studied as well as senescence in perennials such as trees. This review addresses the need for the integration of multi-omics techniques and physiological phenotyping into holistic phenomics approaches to dissect the complex phenomenon of senescence. That became feasible through major advances in the establishment of various, complementary 'omics' technologies. Such an interdisciplinary approach will also need to consider knowledge from the animal field, in particular in relation to novel regulators such as small, non-coding RNAs, epigenetic control and telomere length. Such a characterization of phenotypes via the acquisition of high-dimensional datasets within a systems biology approach will allow us to systematically characterize the various programmes governing senescence beyond leaf senescence in Arabidopsis and to elucidate the underlying molecular processes. Such a multi-omics approach is expected to also spur the application of results from model plants to agriculture and their verification for sustainable and environmentally friendly improvement of crop plant stress resilience and productivity and contribute to improvements based on postharvest physiology for the food industry and the benefit of its customers. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Decomposing phenotype descriptions for the human skeletal phenome.

PubMed

Groza, Tudor; Hunter, Jane; Zankl, Andreas

2013-01-01

Over the course of the last few years there has been a significant amount of research performed on ontology-based formalization of phenotype descriptions. The intrinsic value and knowledge captured within such descriptions can only be expressed by taking advantage of their inner structure that implicitly combines qualities and anatomical entities. We present a meta-model (the Phenotype Fragment Ontology) and a processing pipeline that enable together the automatic decomposition and conceptualization of phenotype descriptions for the human skeletal phenome. We use this approach to showcase the usefulness of the generic concept of phenotype decomposition by performing an experimental study on all skeletal phenotype concepts defined in the Human Phenotype Ontology.

Hypothesis exploration with visualization of variance

PubMed Central

2014-01-01

Background The Consortium for Neuropsychiatric Phenomics (CNP) at UCLA was an investigation into the biological bases of traits such as memory and response inhibition phenotypes—to explore whether they are linked to syndromes including ADHD, Bipolar disorder, and Schizophrenia. An aim of the consortium was in moving from traditional categorical approaches for psychiatric syndromes towards more quantitative approaches based on large-scale analysis of the space of human variation. It represented an application of phenomics—wide-scale, systematic study of phenotypes—to neuropsychiatry research. Results This paper reports on a system for exploration of hypotheses in data obtained from the LA2K, LA3C, and LA5C studies in CNP. ViVA is a system for exploratory data analysis using novel mathematical models and methods for visualization of variance. An example of these methods is called VISOVA, a combination of visualization and analysis of variance, with the flavor of exploration associated with ANOVA in biomedical hypothesis generation. It permits visual identification of phenotype profiles—patterns of values across phenotypes—that characterize groups. Visualization enables screening and refinement of hypotheses about variance structure of sets of phenotypes. Conclusions The ViVA system was designed for exploration of neuropsychiatric hypotheses by interdisciplinary teams. Automated visualization in ViVA supports ‘natural selection’ on a pool of hypotheses, and permits deeper understanding of the statistical architecture of the data. Large-scale perspective of this kind could lead to better neuropsychiatric diagnostics. PMID:25097666

Comparative multi-omics systems analysis of Escherichia coli strains B and K-12.

PubMed

Yoon, Sung Ho; Han, Mee-Jung; Jeong, Haeyoung; Lee, Choong Hoon; Xia, Xiao-Xia; Lee, Dae-Hee; Shim, Ji Hoon; Lee, Sang Yup; Oh, Tae Kwang; Kim, Jihyun F

2012-05-25

Elucidation of a genotype-phenotype relationship is critical to understand an organism at the whole-system level. Here, we demonstrate that comparative analyses of multi-omics data combined with a computational modeling approach provide a framework for elucidating the phenotypic characteristics of organisms whose genomes are sequenced. We present a comprehensive analysis of genome-wide measurements incorporating multifaceted holistic data - genome, transcriptome, proteome, and phenome - to determine the differences between Escherichia coli B and K-12 strains. A genome-scale metabolic network of E. coli B was reconstructed and used to identify genetic bases of the phenotypes unique to B compared with K-12 through in silico complementation testing. This systems analysis revealed that E. coli B is well-suited for production of recombinant proteins due to a greater capacity for amino acid biosynthesis, fewer proteases, and lack of flagella. Furthermore, E. coli B has an additional type II secretion system and a different cell wall and outer membrane composition predicted to be more favorable for protein secretion. In contrast, E. coli K-12 showed a higher expression of heat shock genes and was less susceptible to certain stress conditions. This integrative systems approach provides a high-resolution system-wide view and insights into why two closely related strains of E. coli, B and K-12, manifest distinct phenotypes. Therefore, systematic understanding of cellular physiology and metabolism of the strains is essential not only to determine culture conditions but also to design recombinant hosts.

Comparative multi-omics systems analysis of Escherichia coli strains B and K-12

PubMed Central

2012-01-01

Background Elucidation of a genotype-phenotype relationship is critical to understand an organism at the whole-system level. Here, we demonstrate that comparative analyses of multi-omics data combined with a computational modeling approach provide a framework for elucidating the phenotypic characteristics of organisms whose genomes are sequenced. Results We present a comprehensive analysis of genome-wide measurements incorporating multifaceted holistic data - genome, transcriptome, proteome, and phenome - to determine the differences between Escherichia coli B and K-12 strains. A genome-scale metabolic network of E. coli B was reconstructed and used to identify genetic bases of the phenotypes unique to B compared with K-12 through in silico complementation testing. This systems analysis revealed that E. coli B is well-suited for production of recombinant proteins due to a greater capacity for amino acid biosynthesis, fewer proteases, and lack of flagella. Furthermore, E. coli B has an additional type II secretion system and a different cell wall and outer membrane composition predicted to be more favorable for protein secretion. In contrast, E. coli K-12 showed a higher expression of heat shock genes and was less susceptible to certain stress conditions. Conclusions This integrative systems approach provides a high-resolution system-wide view and insights into why two closely related strains of E. coli, B and K-12, manifest distinct phenotypes. Therefore, systematic understanding of cellular physiology and metabolism of the strains is essential not only to determine culture conditions but also to design recombinant hosts. PMID:22632713

A new genus of horse from Pleistocene North America

PubMed Central

Zazula, Grant D; MacPhee, Ross DE; Scott, Eric; Cahill, James A; McHorse, Brianna K; Kapp, Joshua D; Stiller, Mathias; Wooller, Matthew J; Orlando, Ludovic; Southon, John; Froese, Duane G

2017-01-01

The extinct ‘New World stilt-legged’, or NWSL, equids constitute a perplexing group of Pleistocene horses endemic to North America. Their slender distal limb bones resemble those of Asiatic asses, such as the Persian onager. Previous palaeogenetic studies, however, have suggested a closer relationship to caballine horses than to Asiatic asses. Here, we report complete mitochondrial and partial nuclear genomes from NWSL equids from across their geographic range. Although multiple NWSL equid species have been named, our palaeogenomic and morphometric analyses support the idea that there was only a single species of middle to late Pleistocene NWSL equid, and demonstrate that it falls outside of crown group Equus. We therefore propose a new genus, Haringtonhippus, for the sole species H. francisci. Our combined genomic and phenomic approach to resolving the systematics of extinct megafauna will allow for an improved understanding of the full extent of the terminal Pleistocene extinction event. PMID:29182148

Birth month affects lifetime disease risk: a phenome-wide method

PubMed Central

Boland, Mary Regina; Shahn, Zachary; Madigan, David; Hripcsak, George; Tatonetti, Nicholas P

2015-01-01

Objective An individual’s birth month has a significant impact on the diseases they develop during their lifetime. Previous studies reveal relationships between birth month and several diseases including atherothrombosis, asthma, attention deficit hyperactivity disorder, and myopia, leaving most diseases completely unexplored. This retrospective population study systematically explores the relationship between seasonal affects at birth and lifetime disease risk for 1688 conditions. Methods We developed a hypothesis-free method that minimizes publication and disease selection biases by systematically investigating disease-birth month patterns across all conditions. Our dataset includes 1 749 400 individuals with records at New York-Presbyterian/Columbia University Medical Center born between 1900 and 2000 inclusive. We modeled associations between birth month and 1688 diseases using logistic regression. Significance was tested using a chi-squared test with multiplicity correction. Results We found 55 diseases that were significantly dependent on birth month. Of these 19 were previously reported in the literature (P < .001), 20 were for conditions with close relationships to those reported, and 16 were previously unreported. We found distinct incidence patterns across disease categories. Conclusions Lifetime disease risk is affected by birth month. Seasonally dependent early developmental mechanisms may play a role in increasing lifetime risk of disease. PMID:26041386

PGP repository: a plant phenomics and genomics data publication infrastructure

PubMed Central

Arend, Daniel; Junker, Astrid; Scholz, Uwe; Schüler, Danuta; Wylie, Juliane; Lange, Matthias

2016-01-01

Plant genomics and phenomics represents the most promising tools for accelerating yield gains and overcoming emerging crop productivity bottlenecks. However, accessing this wealth of plant diversity requires the characterization of this material using state-of-the-art genomic, phenomic and molecular technologies and the release of subsequent research data via a long-term stable, open-access portal. Although several international consortia and public resource centres offer services for plant research data management, valuable digital assets remains unpublished and thus inaccessible to the scientific community. Recently, the Leibniz Institute of Plant Genetics and Crop Plant Research and the German Plant Phenotyping Network have jointly initiated the Plant Genomics and Phenomics Research Data Repository (PGP) as infrastructure to comprehensively publish plant research data. This covers in particular cross-domain datasets that are not being published in central repositories because of its volume or unsupported data scope, like image collections from plant phenotyping and microscopy, unfinished genomes, genotyping data, visualizations of morphological plant models, data from mass spectrometry as well as software and documents. The repository is hosted at Leibniz Institute of Plant Genetics and Crop Plant Research using e!DAL as software infrastructure and a Hierarchical Storage Management System as data archival backend. A novel developed data submission tool was made available for the consortium that features a high level of automation to lower the barriers of data publication. After an internal review process, data are published as citable digital object identifiers and a core set of technical metadata is registered at DataCite. The used e!DAL-embedded Web frontend generates for each dataset a landing page and supports an interactive exploration. PGP is registered as research data repository at BioSharing.org, re3data.org and OpenAIRE as valid EU Horizon 2020 open data archive. Above features, the programmatic interface and the support of standard metadata formats, enable PGP to fulfil the FAIR data principles—findable, accessible, interoperable, reusable. Database URL: http://edal.ipk-gatersleben.de/repos/pgp/ PMID:27087305

Alternative polyadenylation drives genome-to-phenome information detours in the AMPKα1 and AMPKα2 knockout mice.

PubMed

Zhang, Shuwen; Zhang, Yangzi; Zhou, Xiang; Fu, Xing; Michal, Jennifer J; Ji, Guoli; Du, Min; Davis, Jon F; Jiang, Zhihua

2018-04-24

Currently available mouse knockout (KO) lines remain largely uncharacterized for genome-to-phenome (G2P) information flows. Here we test our hypothesis that altered myogenesis seen in AMPKα1- and AMPKα2-KO mice is caused by use of alternative polyadenylation sites (APSs). AMPKα1 and AMPKα2 are two α subunits of adenosine monophosphate-activated protein kinase (AMPK), which serves as a cellular sensor in regulation of many biological events. A total of 56,483 APSs were derived from gastrocnemius muscles. The differentially expressed APSs (DE-APSs) that were down-regulated tended to be distal. The DE-APSs that were related to reduced and increased muscle mass were down-regulated in AMPKα1-KO mice, but up-regulated in AMPKα2-KO mice, respectively. Five genes: Car3 (carbonic anhydrase 3), Mylk4 (myosin light chain kinase family, member 4), Neb (nebulin), Obscn (obscurin) and Pfkm (phosphofructokinase, muscle) utilized different APSs with potentially antagonistic effects on muscle function. Overall, gene knockout triggers genome plasticity via use of APSs, completing the G2P processes. However, gene-based analysis failed to reach such a resolution. Therefore, we propose that alternative transcripts are minimal functional units in genomes and the traditional central dogma concept should be now examined under a systems biology approach.

Digital imaging of root traits (DIRT): a high-throughput computing and collaboration platform for field-based root phenomics.

PubMed

Das, Abhiram; Schneider, Hannah; Burridge, James; Ascanio, Ana Karine Martinez; Wojciechowski, Tobias; Topp, Christopher N; Lynch, Jonathan P; Weitz, Joshua S; Bucksch, Alexander

2015-01-01

Plant root systems are key drivers of plant function and yield. They are also under-explored targets to meet global food and energy demands. Many new technologies have been developed to characterize crop root system architecture (CRSA). These technologies have the potential to accelerate the progress in understanding the genetic control and environmental response of CRSA. Putting this potential into practice requires new methods and algorithms to analyze CRSA in digital images. Most prior approaches have solely focused on the estimation of root traits from images, yet no integrated platform exists that allows easy and intuitive access to trait extraction and analysis methods from images combined with storage solutions linked to metadata. Automated high-throughput phenotyping methods are increasingly used in laboratory-based efforts to link plant genotype with phenotype, whereas similar field-based studies remain predominantly manual low-throughput. Here, we present an open-source phenomics platform "DIRT", as a means to integrate scalable supercomputing architectures into field experiments and analysis pipelines. DIRT is an online platform that enables researchers to store images of plant roots, measure dicot and monocot root traits under field conditions, and share data and results within collaborative teams and the broader community. The DIRT platform seamlessly connects end-users with large-scale compute "commons" enabling the estimation and analysis of root phenotypes from field experiments of unprecedented size. DIRT is an automated high-throughput computing and collaboration platform for field based crop root phenomics. The platform is accessible at http://www.dirt.iplantcollaborative.org/ and hosted on the iPlant cyber-infrastructure using high-throughput grid computing resources of the Texas Advanced Computing Center (TACC). DIRT is a high volume central depository and high-throughput RSA trait computation platform for plant scientists working on crop roots. It enables scientists to store, manage and share crop root images with metadata and compute RSA traits from thousands of images in parallel. It makes high-throughput RSA trait computation available to the community with just a few button clicks. As such it enables plant scientists to spend more time on science rather than on technology. All stored and computed data is easily accessible to the public and broader scientific community. We hope that easy data accessibility will attract new tool developers and spur creative data usage that may even be applied to other fields of science.

Harmonising phenomics information for a better interoperability in the rare disease field.

PubMed

Maiella, Sylvie; Olry, Annie; Hanauer, Marc; Lanneau, Valérie; Lourghi, Halima; Donadille, Bruno; Rodwell, Charlotte; Köhler, Sebastian; Seelow, Dominik; Jupp, Simon; Parkinson, Helen; Groza, Tudor; Brudno, Michael; Robinson, Peter N; Rath, Ana

2018-02-07

HIPBI-RD (Harmonising phenomics information for a better interoperability in the rare disease field) is a three-year project which started in 2016 funded via the E-Rare 3 ERA-NET program. This project builds on three resources largely adopted by the rare disease (RD) community: Orphanet, its ontology ORDO (the Orphanet Rare Disease Ontology), HPO (the Human Phenotype Ontology) as well as PhenoTips software for the capture and sharing of structured phenotypic data for RD patients. Our project is further supported by resources developed by the European Bioinformatics Institute and the Garvan Institute. HIPBI-RD aims to provide the community with an integrated, RD-specific bioinformatics ecosystem that will harmonise the way phenomics information is stored in databases and patient files worldwide, and thereby contribute to interoperability. This ecosystem will consist of a suite of tools and ontologies, optimized to work together, and made available through commonly used software repositories. The project workplan follows three main objectives: The HIPBI-RD ecosystem will contribute to the interpretation of variants identified through exome and full genome sequencing by harmonising the way phenotypic information is collected, thus improving diagnostics and delineation of RD. The ultimate goal of HIPBI-RD is to provide a resource that will contribute to bridging genome-scale biology and a disease-centered view on human pathobiology. Achievements in Year 1. Copyright © 2018. Published by Elsevier Masson SAS.

Birth month affects lifetime disease risk: a phenome-wide method.

PubMed

Boland, Mary Regina; Shahn, Zachary; Madigan, David; Hripcsak, George; Tatonetti, Nicholas P

2015-09-01

An individual's birth month has a significant impact on the diseases they develop during their lifetime. Previous studies reveal relationships between birth month and several diseases including atherothrombosis, asthma, attention deficit hyperactivity disorder, and myopia, leaving most diseases completely unexplored. This retrospective population study systematically explores the relationship between seasonal affects at birth and lifetime disease risk for 1688 conditions. We developed a hypothesis-free method that minimizes publication and disease selection biases by systematically investigating disease-birth month patterns across all conditions. Our dataset includes 1 749 400 individuals with records at New York-Presbyterian/Columbia University Medical Center born between 1900 and 2000 inclusive. We modeled associations between birth month and 1688 diseases using logistic regression. Significance was tested using a chi-squared test with multiplicity correction. We found 55 diseases that were significantly dependent on birth month. Of these 19 were previously reported in the literature (P < .001), 20 were for conditions with close relationships to those reported, and 16 were previously unreported. We found distinct incidence patterns across disease categories. Lifetime disease risk is affected by birth month. Seasonally dependent early developmental mechanisms may play a role in increasing lifetime risk of disease. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association.

PGP repository: a plant phenomics and genomics data publication infrastructure.

PubMed

Arend, Daniel; Junker, Astrid; Scholz, Uwe; Schüler, Danuta; Wylie, Juliane; Lange, Matthias

2016-01-01

Plant genomics and phenomics represents the most promising tools for accelerating yield gains and overcoming emerging crop productivity bottlenecks. However, accessing this wealth of plant diversity requires the characterization of this material using state-of-the-art genomic, phenomic and molecular technologies and the release of subsequent research data via a long-term stable, open-access portal. Although several international consortia and public resource centres offer services for plant research data management, valuable digital assets remains unpublished and thus inaccessible to the scientific community. Recently, the Leibniz Institute of Plant Genetics and Crop Plant Research and the German Plant Phenotyping Network have jointly initiated the Plant Genomics and Phenomics Research Data Repository (PGP) as infrastructure to comprehensively publish plant research data. This covers in particular cross-domain datasets that are not being published in central repositories because of its volume or unsupported data scope, like image collections from plant phenotyping and microscopy, unfinished genomes, genotyping data, visualizations of morphological plant models, data from mass spectrometry as well as software and documents.The repository is hosted at Leibniz Institute of Plant Genetics and Crop Plant Research using e!DAL as software infrastructure and a Hierarchical Storage Management System as data archival backend. A novel developed data submission tool was made available for the consortium that features a high level of automation to lower the barriers of data publication. After an internal review process, data are published as citable digital object identifiers and a core set of technical metadata is registered at DataCite. The used e!DAL-embedded Web frontend generates for each dataset a landing page and supports an interactive exploration. PGP is registered as research data repository at BioSharing.org, re3data.org and OpenAIRE as valid EU Horizon 2020 open data archive. Above features, the programmatic interface and the support of standard metadata formats, enable PGP to fulfil the FAIR data principles-findable, accessible, interoperable, reusable.Database URL:http://edal.ipk-gatersleben.de/repos/pgp/. © The Author(s) 2016. Published by Oxford University Press.

Leaf-GP: an open and automated software application for measuring growth phenotypes for arabidopsis and wheat.

PubMed

Zhou, Ji; Applegate, Christopher; Alonso, Albor Dobon; Reynolds, Daniel; Orford, Simon; Mackiewicz, Michal; Griffiths, Simon; Penfield, Steven; Pullen, Nick

2017-01-01

Plants demonstrate dynamic growth phenotypes that are determined by genetic and environmental factors. Phenotypic analysis of growth features over time is a key approach to understand how plants interact with environmental change as well as respond to different treatments. Although the importance of measuring dynamic growth traits is widely recognised, available open software tools are limited in terms of batch image processing, multiple traits analyses, software usability and cross-referencing results between experiments, making automated phenotypic analysis problematic. Here, we present Leaf-GP (Growth Phenotypes), an easy-to-use and open software application that can be executed on different computing platforms. To facilitate diverse scientific communities, we provide three software versions, including a graphic user interface (GUI) for personal computer (PC) users, a command-line interface for high-performance computer (HPC) users, and a well-commented interactive Jupyter Notebook (also known as the iPython Notebook) for computational biologists and computer scientists. The software is capable of extracting multiple growth traits automatically from large image datasets. We have utilised it in Arabidopsis thaliana and wheat ( Triticum aestivum ) growth studies at the Norwich Research Park (NRP, UK). By quantifying a number of growth phenotypes over time, we have identified diverse plant growth patterns between different genotypes under several experimental conditions. As Leaf-GP has been evaluated with noisy image series acquired by different imaging devices (e.g. smartphones and digital cameras) and still produced reliable biological outputs, we therefore believe that our automated analysis workflow and customised computer vision based feature extraction software implementation can facilitate a broader plant research community for their growth and development studies. Furthermore, because we implemented Leaf-GP based on open Python-based computer vision, image analysis and machine learning libraries, we believe that our software not only can contribute to biological research, but also demonstrates how to utilise existing open numeric and scientific libraries (e.g. Scikit-image, OpenCV, SciPy and Scikit-learn) to build sound plant phenomics analytic solutions, in a efficient and effective way. Leaf-GP is a sophisticated software application that provides three approaches to quantify growth phenotypes from large image series. We demonstrate its usefulness and high accuracy based on two biological applications: (1) the quantification of growth traits for Arabidopsis genotypes under two temperature conditions; and (2) measuring wheat growth in the glasshouse over time. The software is easy-to-use and cross-platform, which can be executed on Mac OS, Windows and HPC, with open Python-based scientific libraries preinstalled. Our work presents the advancement of how to integrate computer vision, image analysis, machine learning and software engineering in plant phenomics software implementation. To serve the plant research community, our modulated source code, detailed comments, executables (.exe for Windows; .app for Mac), and experimental results are freely available at https://github.com/Crop-Phenomics-Group/Leaf-GP/releases.

Integrated analysis of phenome, genome, and transcriptome of hybrid rice uncovered multiple heterosis-related loci for yield increase

PubMed Central

Li, Dayong; Huang, Zhiyuan; Song, Shuhui; Xin, Yeyun; Mao, Donghai; Lv, Qiming; Zhou, Ming; Tian, Dongmei; Tang, Mingfeng; Wu, Qi; Liu, Xue; Chen, Tingting; Song, Xianwei; Fu, Xiqin; Zhao, Bingran; Liang, Chengzhi; Li, Aihong; Liu, Guozhen; Li, Shigui; Hu, Songnian; Cao, Xiaofeng; Yu, Jun; Yuan, Longping; Chen, Caiyan; Zhu, Lihuang

2016-01-01

Hybrid rice is the dominant form of rice planted in China, and its use has extended worldwide since the 1970s. It offers great yield advantages and has contributed greatly to the world’s food security. However, the molecular mechanisms underlying heterosis have remained a mystery. In this study we integrated genetics and omics analyses to determine the candidate genes for yield heterosis in a model two-line rice hybrid system, Liang-you-pei 9 (LYP9) and its parents. Phenomics study revealed that the better parent heterosis (BPH) of yield in hybrid is not ascribed to BPH of all the yield components but is specific to the BPH of spikelet number per panicle (SPP) and paternal parent heterosis (PPH) of effective panicle number (EPN). Genetic analyses then identified multiple quantitative trait loci (QTLs) for these two components. Moreover, a number of differentially expressed genes and alleles in the hybrid were mapped by transcriptome profiling to the QTL regions as possible candidate genes. In parallel, a major QTL for yield heterosis, rice heterosis 8 (RH8), was found to be the DTH8/Ghd8/LHD1 gene. Based on the shared allelic heterozygosity of RH8 in many hybrid rice cultivars, a common mechanism for yield heterosis in the present commercial hybrid rice is proposed. PMID:27663737

Deep functional analysis of synII, a 770 kb synthetic yeast chromosome

PubMed Central

Gao, Feng; Gong, Jianhui; Abramczyk, Dariusz; Walker, Roy; Zhao, Hongcui; Chen, Shihong; Liu, Wei; Luo, Yisha; Müller, Carolin A.; Paul-Dubois-Taine, Adrien; Alver, Bonnie; Stracquadanio, Giovanni; Mitchell, Leslie A.; Luo, Zhouqing; Fan, Yanqun; Zhou, Baojin; Wen, Bo; Tan, Fengji; Wang, Yujia; Zi, Jin; Xie, Zexiong; Li, Bingzhi; Yang, Kun; Richardson, Sarah M.; Jiang, Hui; French, Christopher E.; Nieduszynski, Conrad A.; Koszul, Romain; Marston, Adele L.; Yuan, Yingjin; Wang, Jian; Bader, Joel S.; Dai, Junbiao; Boeke, Jef D.; Xu, Xun; Cai, Yizhi; Yang, Huanming

2017-01-01

Herein we report the successful design, construction and characterization of a 770 kb synthetic yeast chromosome II (synII). Our study incorporates characterization at multiple levels, including phenomics, transcriptomics, proteomics, chromosome segregation and replication analysis to provide a thorough and comprehensive analysis of a synthetic chromosome. Our “Trans-Omics” analyses reveal a modest but potentially significant pervasive up-regulation of translational machinery observed in synII is mainly caused by the deletion of 13 tRNAs. By both complementation assays and SCRaMbLE, we targeted and debuged the origin of a growth defect at 37°C in glycerol medium, which is related to misregulation of the HOG response. Despite the subtle differences, the synII strain shows highly consistent biological processes comparable to the native strain. PMID:28280153

An ontology approach to comparative phenomics in plants

USDA-ARS?s Scientific Manuscript database

Plant phenotypes (observable characteristics) are described using many different formats and specialized vocabularies or "ontologies". Similar phenotypes in different species may be given different names. These differences in terms complicate phenotype comparisons across species. This research descr...

Raspberry Pi-powered imaging for plant phenotyping.

PubMed

Tovar, Jose C; Hoyer, J Steen; Lin, Andy; Tielking, Allison; Callen, Steven T; Elizabeth Castillo, S; Miller, Michael; Tessman, Monica; Fahlgren, Noah; Carrington, James C; Nusinow, Dmitri A; Gehan, Malia A

2018-03-01

Image-based phenomics is a powerful approach to capture and quantify plant diversity. However, commercial platforms that make consistent image acquisition easy are often cost-prohibitive. To make high-throughput phenotyping methods more accessible, low-cost microcomputers and cameras can be used to acquire plant image data. We used low-cost Raspberry Pi computers and cameras to manage and capture plant image data. Detailed here are three different applications of Raspberry Pi-controlled imaging platforms for seed and shoot imaging. Images obtained from each platform were suitable for extracting quantifiable plant traits (e.g., shape, area, height, color) en masse using open-source image processing software such as PlantCV. This protocol describes three low-cost platforms for image acquisition that are useful for quantifying plant diversity. When coupled with open-source image processing tools, these imaging platforms provide viable low-cost solutions for incorporating high-throughput phenomics into a wide range of research programs.

Phenomics in Autoimmune and Inflammatory Diseases

ClinicalTrials.gov

2016-12-12

Healthy Volunteer; Rheumatoid Arthritis; Ankylosing Spondylitis; Systemic Lupus Erythematosus/Antiphospholipid Syndrome; FMF; Cryopyrin-Associated Periodic Syndromes /TNF-receptor Associated Periodic Syndrome; Vasculitis; Uveitis; Myositis; Crohn's Disease; Ulcerative Rectocolitis; Type 1 Diabetes; Unclassified IAD Knee and/or Hip Arthritis, Muscular Dystrophy

Culturomics: A New Kid on the Block of OMICS to Enable Personalized Medicine.

PubMed

Kambouris, Manousos E; Pavlidis, Cristiana; Skoufas, Efthymios; Arabatzis, Michael; Kantzanou, Maria; Velegraki, Aristea; Patrinos, George P

2018-02-01

This innovation analysis highlights the underestimated and versatile potential of the new field of culturomics and examines its relation to other OMICS system sciences such as infectiomics, metabolomics, phenomics, and pharmacomicrobiomics. The advent of molecular biology, followed by the emergence of various disciplines of the genomics, and most importantly metagenomics, brought about the sharp decline of conventional microbiology methods. Emergence of culturomics has a natural synergy with therapeutic and clinical genomic approaches so as to realize personalized medicine. Notably, the concept of culturomics expands on that of phenomics and allows a reintroduction of the culture-based phenotypic characterization into the 21st century research repertoire, bolstered by robust technology for automated and massive execution, but its potential is largely unappreciated at present; the few available references show unenthusiastic pursuit and in narrow applications. This has not to be so: depending on the specific brand of culturomics, the scope of applications may extend to medicine, agriculture, environmental sciences, pharmacomicrobiomics, and biotechnology innovation. Moreover, culturomics may produce Big Data. This calls for a new generation of data scientists and innovative ways of harnessing and valorizing Big Data beyond classical genomics. Much more detailed and objective classification and identification of microbiota may soon be at hand through culturomics, thus enabling precision diagnosis toward truly personalized medicine. Culturomics may both widen the scope of microbiology and improve its contributions to diagnostics and personalized medicine, characterizing microbes and determining their associations with health and disease dynamics.

Dissociative Ionization and Product Distributions of Benzene and Pyridine by Electron Impact

NASA Technical Reports Server (NTRS)

Dateo, Christopher E.; Huo, Winifred M.; Fletcher, Graham D.

2003-01-01

We report a theoretical study of the dissociative ionization (DI) and product distributions of benzene (C6H6) and pyridine (C5H5N) from their low-lying ionization channels. Our approach makes use of the fact that electronic motion is much faster than nuclear motion allowing DI to be treated as a two-step process. The first step is the electron-impact ionization resulting in an ion with the same nuclear geometry as the neutral molecule. In the second step, the nuclei relax from the initial geometry and undergo unimolecular dissociation. For the ionization process we use the improved binary-encounter dipole (iBED) model [W.M. Huo, Phys. Rev. A64,042719-I (2001)]. For the unimolecular dissociation, we use multiconfigurational self-consistent field (MCSCF) methods to determine the steepest descent pathways to the possible product channels. More accurate methods are then used to obtain better energetics of the paths which are used to determine unimolecular dissociation probabilities and product distributions. Our analysis of the dissociation products and the thresholds of their productions for benzene are compared with the recent dissociative photoionization meausurements of benzene by Feng et al. [R. Feng, G. Cooper, C.E. Brion, J. Electron Spectrosc. Relat. Phenom. 123,211 (2002)] and the dissociative photoionization measurements of pyridine by Tixier et al. [S. Tixier, G. Cooper, R. Feng, C.E. Brion, J. Electron Spectrosc. Relat. Phenom. 123,185 (2002)] using dipole (e,e+ion) coincidence spectroscopy.

Coordinated international action to accelerate genome-to-phenome with FAANG, the Functional Annotation of Animal Genomes project.

PubMed

Andersson, Leif; Archibald, Alan L; Bottema, Cynthia D; Brauning, Rudiger; Burgess, Shane C; Burt, Dave W; Casas, Eduardo; Cheng, Hans H; Clarke, Laura; Couldrey, Christine; Dalrymple, Brian P; Elsik, Christine G; Foissac, Sylvain; Giuffra, Elisabetta; Groenen, Martien A; Hayes, Ben J; Huang, LuSheng S; Khatib, Hassan; Kijas, James W; Kim, Heebal; Lunney, Joan K; McCarthy, Fiona M; McEwan, John C; Moore, Stephen; Nanduri, Bindu; Notredame, Cedric; Palti, Yniv; Plastow, Graham S; Reecy, James M; Rohrer, Gary A; Sarropoulou, Elena; Schmidt, Carl J; Silverstein, Jeffrey; Tellam, Ross L; Tixier-Boichard, Michele; Tosser-Klopp, Gwenola; Tuggle, Christopher K; Vilkki, Johanna; White, Stephen N; Zhao, Shuhong; Zhou, Huaijun

2015-03-25

We describe the organization of a nascent international effort, the Functional Annotation of Animal Genomes (FAANG) project, whose aim is to produce comprehensive maps of functional elements in the genomes of domesticated animal species.

Coordinated international action to accelerate genome-to-phenome with FAANG, The Functional Annotation of Animal Genomes project

USDA-ARS?s Scientific Manuscript database

We describe the organization of a nascent international effort - the "Functional Annotation of ANimal Genomes" project - whose aim is to produce comprehensive maps of functional elements in the genomes of domesticated animal species....

Forward phenomics of oat panicles

USDA-ARS?s Scientific Manuscript database

There is a growing need for adapted and more productive germplasm to expand oat production, optimize its yield, improve groat quality, and satisfy farmers and consumers demand, especially in the Upper Midwest of the US. Oat germplasm, representing different eco-geographical origins and breeding stat...

Comparative analyses of population-scale phenomic data in electronic medical records reveal race-specific disease networks

PubMed Central

Glicksberg, Benjamin S.; Li, Li; Badgeley, Marcus A.; Shameer, Khader; Kosoy, Roman; Beckmann, Noam D.; Pho, Nam; Hakenberg, Jörg; Ma, Meng; Ayers, Kristin L.; Hoffman, Gabriel E.; Dan Li, Shuyu; Schadt, Eric E.; Patel, Chirag J.; Chen, Rong; Dudley, Joel T.

2016-01-01

Motivation: Underrepresentation of racial groups represents an important challenge and major gap in phenomics research. Most of the current human phenomics research is based primarily on European populations; hence it is an important challenge to expand it to consider other population groups. One approach is to utilize data from EMR databases that contain patient data from diverse demographics and ancestries. The implications of this racial underrepresentation of data can be profound regarding effects on the healthcare delivery and actionability. To the best of our knowledge, our work is the first attempt to perform comparative, population-scale analyses of disease networks across three different populations, namely Caucasian (EA), African American (AA) and Hispanic/Latino (HL). Results: We compared susceptibility profiles and temporal connectivity patterns for 1988 diseases and 37 282 disease pairs represented in a clinical population of 1 025 573 patients. Accordingly, we revealed appreciable differences in disease susceptibility, temporal patterns, network structure and underlying disease connections between EA, AA and HL populations. We found 2158 significantly comorbid diseases for the EA cohort, 3265 for AA and 672 for HL. We further outlined key disease pair associations unique to each population as well as categorical enrichments of these pairs. Finally, we identified 51 key ‘hub’ diseases that are the focal points in the race-centric networks and of particular clinical importance. Incorporating race-specific disease comorbidity patterns will produce a more accurate and complete picture of the disease landscape overall and could support more precise understanding of disease relationships and patient management towards improved clinical outcomes. Contacts: rong.chen@mssm.edu or joel.dudley@mssm.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27307606

The nutritional phenome of EMT-induced cancer stem-like cells.

PubMed

Cuyàs, Elisabet; Corominas-Faja, Bruna; Menendez, Javier A

2014-06-30

The metabolic features of cancer stem (CS) cells and the effects of specific nutrients or metabolites on CS cells remain mostly unexplored. A preliminary study to delineate the nutritional phenome of CS cells exploited the landmark observation that upon experimental induction into an epithelial-to-mesenchymal (EMT) transition, the proportion of CS-like cells drastically increases within a breast cancer cell population. EMT-induced CS-like cells (HMLERshEcad) and isogenic parental cells (HMLERshCntrol) were simultaneously screened for their ability to generate energy-rich NADH when cultured in a standardized high-throughput metabolic phenotyping platform comprising >350 wells that were pre-loaded with different carbohydrates/starches, alcohols, fatty acids, ketones, carboxylic acids, amino acids, and bi-amino acids. The generation of "phenetic maps" of the carbon and nitrogen utilization patterns revealed that the acquisition of a CS-like cellular state provided an enhanced ability to utilize additional catabolic fuels, especially under starvation conditions. Crucially, the acquisition of cancer stemness activated a metabolic infrastructure that enabled the vectorial transfer of high-energy nutrients such as glycolysis end products (pyruvate, lactate) and bona fide ketone bodies (β-hydroxybutyrate) from the extracellular microenvironment to support mitochondrial energy production in CS-like cells. Metabolic reprogramming may thus constitute an efficient adaptive strategy through which CS-like cells would rapidly obtain an advantage in hostile conditions such as nutrient starvation following the inhibition of tumor angiogenesis. By understanding how specific nutrients could bioenergetically boost EMT-CS-like phenotypes, "smart foods" or systemic "metabolic nichotherapies" may be tailored to specific nutritional CSC phenomes, whereas high-resolution heavy isotope-labeled nutrient tracking may be developed to monitor the spatiotemporal distribution and functionality of CS-like cells in real time.

Comparative functional pan-genome analyses to build connections between genomic dynamics and phenotypic evolution in polycyclic aromatic hydrocarbon metabolism in the genus Mycobacterium.

PubMed

Kweon, Ohgew; Kim, Seong-Jae; Blom, Jochen; Kim, Sung-Kwan; Kim, Bong-Soo; Baek, Dong-Heon; Park, Su Inn; Sutherland, John B; Cerniglia, Carl E

2015-02-14

The bacterial genus Mycobacterium is of great interest in the medical and biotechnological fields. Despite a flood of genome sequencing and functional genomics data, significant gaps in knowledge between genome and phenome seriously hinder efforts toward the treatment of mycobacterial diseases and practical biotechnological applications. In this study, we propose the use of systematic, comparative functional pan-genomic analysis to build connections between genomic dynamics and phenotypic evolution in polycyclic aromatic hydrocarbon (PAH) metabolism in the genus Mycobacterium. Phylogenetic, phenotypic, and genomic information for 27 completely genome-sequenced mycobacteria was systematically integrated to reconstruct a mycobacterial phenotype network (MPN) with a pan-genomic concept at a network level. In the MPN, mycobacterial phenotypes show typical scale-free relationships. PAH degradation is an isolated phenotype with the lowest connection degree, consistent with phylogenetic and environmental isolation of PAH degraders. A series of functional pan-genomic analyses provide conserved and unique types of genomic evidence for strong epistatic and pleiotropic impacts on evolutionary trajectories of the PAH-degrading phenotype. Under strong natural selection, the detailed gene gain/loss patterns from horizontal gene transfer (HGT)/deletion events hypothesize a plausible evolutionary path, an epistasis-based birth and pleiotropy-dependent death, for PAH metabolism in the genus Mycobacterium. This study generated a practical mycobacterial compendium of phenotypic and genomic changes, focusing on the PAH-degrading phenotype, with a pan-genomic perspective of the evolutionary events and the environmental challenges. Our findings suggest that when selection acts on PAH metabolism, only a small fraction of possible trajectories is likely to be observed, owing mainly to a combination of the ambiguous phenotypic effects of PAHs and the corresponding pleiotropy- and epistasis-dependent evolutionary adaptation. Evolutionary constraints on the selection of trajectories, like those seen in PAH-degrading phenotypes, are likely to apply to the evolution of other phenotypes in the genus Mycobacterium.

Systematically linking tranSMART, Galaxy and EGA for reusing human translational research data

PubMed Central

Zhang, Chao; Bijlard, Jochem; Staiger, Christine; Scollen, Serena; van Enckevort, David; Hoogstrate, Youri; Senf, Alexander; Hiltemann, Saskia; Repo, Susanna; Pipping, Wibo; Bierkens, Mariska; Payralbe, Stefan; Stringer, Bas; Heringa, Jaap; Stubbs, Andrew; Bonino Da Silva Santos, Luiz Olavo; Belien, Jeroen; Weistra, Ward; Azevedo, Rita; van Bochove, Kees; Meijer, Gerrit; Boiten, Jan-Willem; Rambla, Jordi; Fijneman, Remond; Spalding, J. Dylan; Abeln, Sanne

2017-01-01

The availability of high-throughput molecular profiling techniques has provided more accurate and informative data for regular clinical studies. Nevertheless, complex computational workflows are required to interpret these data. Over the past years, the data volume has been growing explosively, requiring robust human data management to organise and integrate the data efficiently. For this reason, we set up an ELIXIR implementation study, together with the Translational research IT (TraIT) programme, to design a data ecosystem that is able to link raw and interpreted data. In this project, the data from the TraIT Cell Line Use Case (TraIT-CLUC) are used as a test case for this system. Within this ecosystem, we use the European Genome-phenome Archive (EGA) to store raw molecular profiling data; tranSMART to collect interpreted molecular profiling data and clinical data for corresponding samples; and Galaxy to store, run and manage the computational workflows. We can integrate these data by linking their repositories systematically. To showcase our design, we have structured the TraIT-CLUC data, which contain a variety of molecular profiling data types, for storage in both tranSMART and EGA. The metadata provided allows referencing between tranSMART and EGA, fulfilling the cycle of data submission and discovery; we have also designed a data flow from EGA to Galaxy, enabling reanalysis of the raw data in Galaxy. In this way, users can select patient cohorts in tranSMART, trace them back to the raw data and perform (re)analysis in Galaxy. Our conclusion is that the majority of metadata does not necessarily need to be stored (redundantly) in both databases, but that instead FAIR persistent identifiers should be available for well-defined data ontology levels: study, data access committee, physical sample, data sample and raw data file. This approach will pave the way for the stable linkage and reuse of data. PMID:29123641

Systematically linking tranSMART, Galaxy and EGA for reusing human translational research data.

PubMed

Zhang, Chao; Bijlard, Jochem; Staiger, Christine; Scollen, Serena; van Enckevort, David; Hoogstrate, Youri; Senf, Alexander; Hiltemann, Saskia; Repo, Susanna; Pipping, Wibo; Bierkens, Mariska; Payralbe, Stefan; Stringer, Bas; Heringa, Jaap; Stubbs, Andrew; Bonino Da Silva Santos, Luiz Olavo; Belien, Jeroen; Weistra, Ward; Azevedo, Rita; van Bochove, Kees; Meijer, Gerrit; Boiten, Jan-Willem; Rambla, Jordi; Fijneman, Remond; Spalding, J Dylan; Abeln, Sanne

2017-01-01

The availability of high-throughput molecular profiling techniques has provided more accurate and informative data for regular clinical studies. Nevertheless, complex computational workflows are required to interpret these data. Over the past years, the data volume has been growing explosively, requiring robust human data management to organise and integrate the data efficiently. For this reason, we set up an ELIXIR implementation study, together with the Translational research IT (TraIT) programme, to design a data ecosystem that is able to link raw and interpreted data. In this project, the data from the TraIT Cell Line Use Case (TraIT-CLUC) are used as a test case for this system. Within this ecosystem, we use the European Genome-phenome Archive (EGA) to store raw molecular profiling data; tranSMART to collect interpreted molecular profiling data and clinical data for corresponding samples; and Galaxy to store, run and manage the computational workflows. We can integrate these data by linking their repositories systematically. To showcase our design, we have structured the TraIT-CLUC data, which contain a variety of molecular profiling data types, for storage in both tranSMART and EGA. The metadata provided allows referencing between tranSMART and EGA, fulfilling the cycle of data submission and discovery; we have also designed a data flow from EGA to Galaxy, enabling reanalysis of the raw data in Galaxy. In this way, users can select patient cohorts in tranSMART, trace them back to the raw data and perform (re)analysis in Galaxy. Our conclusion is that the majority of metadata does not necessarily need to be stored (redundantly) in both databases, but that instead FAIR persistent identifiers should be available for well-defined data ontology levels: study, data access committee, physical sample, data sample and raw data file. This approach will pave the way for the stable linkage and reuse of data.

Field-based phenomics for plant genetics research

USDA-ARS?s Scientific Manuscript database

Perhaps the greatest challenge for crop research in the 21st century is how to predict crop performance as a function of genetic architecture and climate change. Advances in “next generation” DNA sequencing have greatly reduced genotyping costs. Methods for characterization of plant traits (phenotyp...

76 FR 52220 - Airworthiness Directives; Embraer-Empresa Brasileira de Aeronautica S.A. (EMBRAER) Model EMB-500...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-22

... Support, Av. Brig. Farina Lima, 2170, Sao Jose dos Campos--SP, CEP: 12227-901--PO Box: 36/2, BRASIL..., BRASIL; telephone: ++55 12 3927-5383; fax: ++55 12 3927-2619; e-mail: embraer.com .br">phenom.reliability...

76 FR 26959 - Airworthiness Directives; Embraer-Embraer-Empresa Brasileira de Aeronautica S.A. (EMBRAER) Model...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-10

...-- SP, CEP: 12227-901--PO Box: 36/2, Brasil; telephone: ++55 12 3927-5383; fax: ++55 12 3927-2619; E...: 36/2, Brasil; telephone: ++55 12 3927-5383; fax: ++55 12 3927-2619; E- mail: phenom.reliability...

Breeding blueberries for a changing global environment: a review

PubMed Central

Lobos, Gustavo A.; Hancock, James F.

2015-01-01

Today, blueberries are recognized worldwide as one of the foremost health foods, becoming one of the crops with the highest productive and commercial projections. Over the last 100 years, the geographical area where highbush blueberries are grown has extended dramatically into hotter and drier environments. The expansion of highbush blueberry growing into warmer regions will be challenged in the future by increases in average global temperature and extreme fluctuations in temperature and rainfall patterns. Considerable genetic variability exists within the blueberry gene pool that breeders can use to meet these challenges, but traditional selection techniques can be slow and inefficient and the precise adaptations of genotypes often remain hidden. Marker assisted breeding (MAB) and phenomics could aid greatly in identifying those individuals carrying adventitious traits, increasing selection efficiency and shortening the rate of cultivar release. While phenomics have begun to be used in the breeding of grain crops in the last 10 years, their use in fruit breeding programs it is almost non-existent. PMID:26483803

MicroCT-based phenomics in the zebrafish skeleton reveals virtues of deep phenotyping in a distributed organ system.

PubMed

Hur, Matthew; Gistelinck, Charlotte A; Huber, Philippe; Lee, Jane; Thompson, Marjorie H; Monstad-Rios, Adrian T; Watson, Claire J; McMenamin, Sarah K; Willaert, Andy; Parichy, David M; Coucke, Paul; Kwon, Ronald Y

2017-09-08

Phenomics, which ideally involves in-depth phenotyping at the whole-organism scale, may enhance our functional understanding of genetic variation. Here, we demonstrate methods to profile hundreds of phenotypic measures comprised of morphological and densitometric traits at a large number of sites within the axial skeleton of adult zebrafish. We show the potential for vertebral patterns to confer heightened sensitivity, with similar specificity, in discriminating mutant populations compared to analyzing individual vertebrae in isolation. We identify phenotypes associated with human brittle bone disease and thyroid stimulating hormone receptor hyperactivity. Finally, we develop allometric models and show their potential to aid in the discrimination of mutant phenotypes masked by alterations in growth. Our studies demonstrate virtues of deep phenotyping in a spatially distributed organ system. Analyzing phenotypic patterns may increase productivity in genetic screens, and facilitate the study of genetic variants associated with smaller effect sizes, such as those that underlie complex diseases.

Phenotyping of Brassica napus for high oil content

USDA-ARS?s Scientific Manuscript database

Multi-trait and multi-growth stage phenotyping may improve our ability to assess the dynamic changes in the B. napus phenome under spatiotemporal field conditions. A minimum set of phenotypic traits that can integrate ontogeny and architecture of Brassica napus L. is required for breeding and select...

In Utero Phthalate Effects in the Female Rat: A Model for MRKH Syndrome

EPA Science Inventory

Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by uterine and vaginal canal aplasia in normal karyotype human females and is a syndrome with poorly define etiology. Reproductive toxicity of phthlate esters (PEs) occurs in rat offspring exposed in utero. a phenome...

Deep functional analysis of synII, a 770-kilobase synthetic yeast chromosome.

PubMed

Shen, Yue; Wang, Yun; Chen, Tai; Gao, Feng; Gong, Jianhui; Abramczyk, Dariusz; Walker, Roy; Zhao, Hongcui; Chen, Shihong; Liu, Wei; Luo, Yisha; Müller, Carolin A; Paul-Dubois-Taine, Adrien; Alver, Bonnie; Stracquadanio, Giovanni; Mitchell, Leslie A; Luo, Zhouqing; Fan, Yanqun; Zhou, Baojin; Wen, Bo; Tan, Fengji; Wang, Yujia; Zi, Jin; Xie, Zexiong; Li, Bingzhi; Yang, Kun; Richardson, Sarah M; Jiang, Hui; French, Christopher E; Nieduszynski, Conrad A; Koszul, Romain; Marston, Adele L; Yuan, Yingjin; Wang, Jian; Bader, Joel S; Dai, Junbiao; Boeke, Jef D; Xu, Xun; Cai, Yizhi; Yang, Huanming

2017-03-10

Here, we report the successful design, construction, and characterization of a 770-kilobase synthetic yeast chromosome II (synII). Our study incorporates characterization at multiple levels-including phenomics, transcriptomics, proteomics, chromosome segregation, and replication analysis-to provide a thorough and comprehensive analysis of a synthetic chromosome. Our Trans-Omics analyses reveal a modest but potentially relevant pervasive up-regulation of translational machinery observed in synII, mainly caused by the deletion of 13 transfer RNAs. By both complementation assays and SCRaMbLE (synthetic chromosome rearrangement and modification by loxP -mediated evolution), we targeted and debugged the origin of a growth defect at 37°C in glycerol medium, which is related to misregulation of the high-osmolarity glycerol response. Despite the subtle differences, the synII strain shows highly consistent biological processes comparable to the native strain. Copyright © 2017, American Association for the Advancement of Science.

Merging genomic and phenomic data for research and clinical impact.

PubMed

Shublaq, Nour W; Coveney, Peter V

2012-01-01

Driven primarily by advances in genomics, pharmacogenomics and systems biology technologies, large amounts of genomic and phenomic data are today being collected on individuals worldwide. Integrative analysis, mining, and computer modeling of these data, facilitated by information technology, have led to the development of predictive, preventive, and personalized medicine. This transformative approach holds the potential inter alia to enable future general practitioners and physicians to prescribe the right drug to the right patient at the right dosage. For such patient-specific medicine to be adopted as standard clinical practice, publicly accumulated knowledge of genes, proteins, molecular functional annotations, and interactions need to be unified and with electronic health records including phenotypic information, most of which still reside as paper-based records in hospitals. We review the state-of-the-art in terms of electronic data capture and medical data standards. Some of these activities are drawn from research projects currently being performed within the European Virtual Physiological Human (VPH) initiative; all are being monitored by the VPH INBIOMEDvision Consortium. Various ethical, legal and societal issues linked with privacy will increasingly arise in the post-genomic era. This will require a closer interaction between the bioinformatics/systems biology and medical informatics/healthcare communities. Planning for how individuals will own their personal health records is urgently needed, as the cost of sequencing a whole human genome will soon be less than U.S. $100. We discuss some of the issues that will need to be addressed by society as a result of this revolution in healthcare.

World Endometriosis Research Foundation Endometriosis Phenome and biobanking harmonization project: II. Clinical and covariate phenotype data collection in endometriosis research

PubMed Central

Vitonis, Allison F.; Vincent, Katy; Rahmioglu, Nilufer; Fassbender, Amelie; Buck Louis, Germaine M.; Hummelshoj, Lone; Giudice, Linda C.; Stratton, Pamela; Adamson, G. David; Becker, Christian M.; Zondervan, Krina T.; Missmer, Stacey A.

2014-01-01

Objective To harmonize the collection of nonsurgical clinical and epidemiologic data relevant to endometriosis research, allowing large-scale collaboration. Design An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries on five continents. Setting In 2013, two workshops followed by global consultation, bringing together 54 leaders in endometriosis research. Patients None. Intervention(s) Development of a self-administered endometriosis patient questionnaire (EPQ), based on [1] systematic comparison of questionnaires from eight centers that collect data from endometriosis cases (and controls/comparison women) on a medium to large scale (publication on >100 cases); [2] literature evidence; and [3] several global consultation rounds. Main Outcome Measure(s) Standard recommended and minimum required questionnaires to capture detailed clinical and covariate data. Result(s) The standard recommended (EPHect EPQ-S) and minimum required (EPHect EPQ-M) questionnaires contain questions on pelvic pain, subfertility and menstrual/reproductive history, hormone/medication use, medical history, and personal information. Conclusion(s) The EPQ captures the basic set of patient characteristics and exposures considered by the WERF EPHect Working Group to be most critical for the advancement of endometriosis research, but is also relevant to other female conditions with similar risk factors and/or symptomatology. The instruments will be reviewed based on feedback from investigators, and–after a first review after 1 year–triannually through systematic follow-up surveys. Updated versions will be made available through http://endometriosisfoundation.org/ephect. PMID:25256930

Genome to phenome mapping in apple using historical data

USDA-ARS?s Scientific Manuscript database

Apple (Malus domestica) is one of the world’s most valuable fruit crops. Its large size and long juvenile phase make it a particularly promising candidate for marker-assisted selection (MAS). However, advances in MAS in apple have been limited by a lack of phenotype and genotype data from sufficien...

Improving wood properties for wood utilization through multi-omics integration in lignin biosynthesis

DOE PAGES

Wang, Jack P.; Matthews, Megan L.; Williams, Cranos M.; ...

2018-04-20

A multi-omics quantitative integrative analysis of lignin biosynthesis can advance the strategic engineering of wood for timber, pulp, and biofuels. Lignin is polymerized from three monomers (monolignols) produced by a grid-like pathway. The pathway in wood formation of Populus trichocarpa has at least 21 genes, encoding enzymes that mediate 37 reactions on 24 metabolites, leading to lignin and affecting wood properties. We perturb these 21 pathway genes and integrate transcriptomic, proteomic, fluxomic and phenomic data from 221 lines selected from ~2000 transgenics (6-month-old). The integrative analysis estimates how changing expression of pathway gene or gene combination affects protein abundance, metabolic-flux,more » metabolite concentrations, and 25 wood traits, including lignin, tree-growth, density, strength, and saccharification. The analysis then predicts improvements in any of these 25 traits individually or in combinations, through engineering expression of specific monolignol genes. The analysis may lead to greater understanding of other pathways for improved growth and adaptation.« less

Improving wood properties for wood utilization through multi-omics integration in lignin biosynthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Jack P.; Matthews, Megan L.; Williams, Cranos M.

A multi-omics quantitative integrative analysis of lignin biosynthesis can advance the strategic engineering of wood for timber, pulp, and biofuels. Lignin is polymerized from three monomers (monolignols) produced by a grid-like pathway. The pathway in wood formation of Populus trichocarpa has at least 21 genes, encoding enzymes that mediate 37 reactions on 24 metabolites, leading to lignin and affecting wood properties. We perturb these 21 pathway genes and integrate transcriptomic, proteomic, fluxomic and phenomic data from 221 lines selected from ~2000 transgenics (6-month-old). The integrative analysis estimates how changing expression of pathway gene or gene combination affects protein abundance, metabolic-flux,more » metabolite concentrations, and 25 wood traits, including lignin, tree-growth, density, strength, and saccharification. The analysis then predicts improvements in any of these 25 traits individually or in combinations, through engineering expression of specific monolignol genes. The analysis may lead to greater understanding of other pathways for improved growth and adaptation.« less

Improving wood properties for wood utilization through multi-omics integration in lignin biosynthesis.

PubMed

Wang, Jack P; Matthews, Megan L; Williams, Cranos M; Shi, Rui; Yang, Chenmin; Tunlaya-Anukit, Sermsawat; Chen, Hsi-Chuan; Li, Quanzi; Liu, Jie; Lin, Chien-Yuan; Naik, Punith; Sun, Ying-Hsuan; Loziuk, Philip L; Yeh, Ting-Feng; Kim, Hoon; Gjersing, Erica; Shollenberger, Todd; Shuford, Christopher M; Song, Jina; Miller, Zachary; Huang, Yung-Yun; Edmunds, Charles W; Liu, Baoguang; Sun, Yi; Lin, Ying-Chung Jimmy; Li, Wei; Chen, Hao; Peszlen, Ilona; Ducoste, Joel J; Ralph, John; Chang, Hou-Min; Muddiman, David C; Davis, Mark F; Smith, Chris; Isik, Fikret; Sederoff, Ronald; Chiang, Vincent L

2018-04-20

A multi-omics quantitative integrative analysis of lignin biosynthesis can advance the strategic engineering of wood for timber, pulp, and biofuels. Lignin is polymerized from three monomers (monolignols) produced by a grid-like pathway. The pathway in wood formation of Populus trichocarpa has at least 21 genes, encoding enzymes that mediate 37 reactions on 24 metabolites, leading to lignin and affecting wood properties. We perturb these 21 pathway genes and integrate transcriptomic, proteomic, fluxomic and phenomic data from 221 lines selected from ~2000 transgenics (6-month-old). The integrative analysis estimates how changing expression of pathway gene or gene combination affects protein abundance, metabolic-flux, metabolite concentrations, and 25 wood traits, including lignin, tree-growth, density, strength, and saccharification. The analysis then predicts improvements in any of these 25 traits individually or in combinations, through engineering expression of specific monolignol genes. The analysis may lead to greater understanding of other pathways for improved growth and adaptation.

Cancer Imaging Phenomics Toolkit (CaPTK) | Informatics Technology for Cancer Research (ITCR)

Cancer.gov

CaPTk is a tool that facilitates translation of highly sophisticated methods that help us gain a comprehensive understanding of the underlying mechanisms of cancer from medical imaging research to the clinic. It replicates basic interactive functionalities of radiological workstations and is distributed under a BSD-style license.

Patterns of genomic and phenomic diversity in wine and table grapes

USDA-ARS?s Scientific Manuscript database

Grapes are one of the most economically and culturally important crops worldwide, and they have been bred for both winemaking and fresh consumption. Here we evaluate patterns of diversity across 33 phenotypes collected over a 17-year period from 580 table and wine grape accessions that belong to one...

A Road Map Towards High pH Adaptability: Phenomic and Genomic Approaches to Azalea Breeding (Rhododendron sp.)

USDA-ARS?s Scientific Manuscript database

A research grant from the Azalea Society of America has enabled us to collect and begin evaluating diverse Rhododendron viscosum germplasm to identify genetic and phenotypic variation for pH adaptability. During the Spring of 2014, we developed novel, in vitro screening methods for Rhododendron to ...

Coordinated effort to advance genomes-to-phenomes through the integration of bioinformatics with aquaculture research

USDA-ARS?s Scientific Manuscript database

Aquaculture is the fastest growing food production system in the world. The research program at the USDA-ARS-SNARC strives to improve the efficiency and sustainability of warmwater U.S. aquaculture. SNARC scientists have impacted the catfish (#1 U.S. aquaculture industry), tilapia (#3) and hybrid st...

Approaches for geospatial processing of field-based high-throughput plant phenomics data from ground vehicle platforms

USDA-ARS?s Scientific Manuscript database

Understanding the genetic basis of complex plant traits requires connecting genotype to phenotype information, known as the “G2P question.” In the last three decades, genotyping methods have become highly developed. Much less innovation has occurred for measuring plant traits (phenotyping), particul...

Stroke Investigative Research and Education Network: Community Engagement and Outreach within Phenomics Core

ERIC Educational Resources Information Center

Jenkins, Carolyn; Arulogun, Oyedunni Sola; Singh, Arti; Mande, Aliyu T.; Ajayi, Eric; Benedict, Calys Tagoe; Ovbiagele, Bruce; Lackland, Daniel T.; Sarfo, Fred Stephen; Akinyemi, Rufus; Akpalu, Albert; Obiako, Reginald; Melikam, Enzinne Sylvia; Laryea, Ruth; Shidali, Vincent; Sagoe, Kwamena; Ibinaiye, Philip; Fakunle, Adekunie Gregory; Owolabi, Lukman F.; Owolabi, Mayowa O.

2016-01-01

Stroke is the leading cause of neurological hospital admissions in sub-Saharan Africa (SSA) and the second leading cause of death globally. The Stroke Investigative Research and Education Network [SIREN] seeks to comprehensively characterize the genomic, sociocultural, economic, and behavioral risk factors for stroke and to build effective teams…

Patterns of genomic and phenomic diversity in wine and table grapes

USDA-ARS?s Scientific Manuscript database

Grapes are one of the most economically and culturally important crops worldwide and they have been bred for both winemaking and fresh consumption. Here we evaluate patterns of diversity across 33 phenotypes collected over a 17-year period from 580 table and wine grape cultivars that belong to one ...

Surpassing the Target: How a Recruitment Campaign Transformed the Participant Accrual Trajectory in the Epilepsy Phenome/Genome Project

PubMed Central

Freyer Karn, Catharine; Fox, Kristen

2015-01-01

Abstract Participant recruitment challenges pervade the majority of publicly funded clinical trials. However, little is known about methods for enhancing participant accrual. The Epilepsy Phenome/Genome Project (EPGP), a multicenter study funded by the National Institute of Neurological Disorders and Stroke (NINDS), aimed to enroll a total of 5,250 participants to better understand the genetic causes and phenotypic manifestations of epilepsy. However, similar to other trials, EPGP encountered recruitment challenges, and by the end of its first year, net enrollment was only 48% of the target for that time. To address this, EPGP established a National Participant Recruitment Campaign and began implementing and tracking the enrollment outcomes of a variety of proven and relatively novel recruitment methods. At the conclusion of the project, EPGP had successfully enrolled a total of 5,445 participants, thus surpassing its enrollment target. Data pertaining to EPGP's National Participant Recruitment Campaign was analyzed retrospectively, and the results are reported here, so that other multicenter trials may consider these methods in their recruitment planning and potentially avoid the costly repercussions of participant accrual issues. PMID:26176343

Getting ready for the Human Phenome Project: the 2012 forum of the Human Variome Project.

PubMed

Oetting, William S; Robinson, Peter N; Greenblatt, Marc S; Cotton, Richard G; Beck, Tim; Carey, John C; Doelken, Sandra C; Girdea, Marta; Groza, Tudor; Hamilton, Carol M; Hamosh, Ada; Kerner, Berit; MacArthur, Jacqueline A L; Maglott, Donna R; Mons, Barend; Rehm, Heidi L; Schofield, Paul N; Searle, Beverly A; Smedley, Damian; Smith, Cynthia L; Bernstein, Inge Thomsen; Zankl, Andreas; Zhao, Eric Y

2013-04-01

A forum of the Human Variome Project (HVP) was held as a satellite to the 2012 Annual Meeting of the American Society of Human Genetics in San Francisco, California. The theme of this meeting was "Getting Ready for the Human Phenome Project." Understanding the genetic contribution to both rare single-gene "Mendelian" disorders and more complex common diseases will require integration of research efforts among many fields and better defined phenotypes. The HVP is dedicated to bringing together researchers and research populations throughout the world to provide the resources to investigate the impact of genetic variation on disease. To this end, there needs to be a greater sharing of phenotype and genotype data. For this to occur, many databases that currently exist will need to become interoperable to allow for the combining of cohorts with similar phenotypes to increase statistical power for studies attempting to identify novel disease genes or causative genetic variants. Improved systems and tools that enhance the collection of phenotype data from clinicians are urgently needed. This meeting begins the HVP's effort toward this important goal. © 2013 Wiley Periodicals, Inc.

A novel mesh processing based technique for 3D plant analysis

PubMed Central

2012-01-01

Background In recent years, imaging based, automated, non-invasive, and non-destructive high-throughput plant phenotyping platforms have become popular tools for plant biology, underpinning the field of plant phenomics. Such platforms acquire and record large amounts of raw data that must be accurately and robustly calibrated, reconstructed, and analysed, requiring the development of sophisticated image understanding and quantification algorithms. The raw data can be processed in different ways, and the past few years have seen the emergence of two main approaches: 2D image processing and 3D mesh processing algorithms. Direct image quantification methods (usually 2D) dominate the current literature due to comparative simplicity. However, 3D mesh analysis provides the tremendous potential to accurately estimate specific morphological features cross-sectionally and monitor them over-time. Result In this paper, we present a novel 3D mesh based technique developed for temporal high-throughput plant phenomics and perform initial tests for the analysis of Gossypium hirsutum vegetative growth. Based on plant meshes previously reconstructed from multi-view images, the methodology involves several stages, including morphological mesh segmentation, phenotypic parameters estimation, and plant organs tracking over time. The initial study focuses on presenting and validating the accuracy of the methodology on dicotyledons such as cotton but we believe the approach will be more broadly applicable. This study involved applying our technique to a set of six Gossypium hirsutum (cotton) plants studied over four time-points. Manual measurements, performed for each plant at every time-point, were used to assess the accuracy of our pipeline and quantify the error on the morphological parameters estimated. Conclusion By directly comparing our automated mesh based quantitative data with manual measurements of individual stem height, leaf width and leaf length, we obtained the mean absolute errors of 9.34%, 5.75%, 8.78%, and correlation coefficients 0.88, 0.96, and 0.95 respectively. The temporal matching of leaves was accurate in 95% of the cases and the average execution time required to analyse a plant over four time-points was 4.9 minutes. The mesh processing based methodology is thus considered suitable for quantitative 4D monitoring of plant phenotypic features. PMID:22553969

Chimera patterns in the Kuramoto-Battogtokh model

NASA Astrophysics Data System (ADS)

Smirnov, Lev; Osipov, Grigory; Pikovsky, Arkady

2017-02-01

Kuramoto and Battogtokh (2002 Nonlinear Phenom. Complex Syst. 5 380) discovered chimera states represented by stable coexisting synchrony and asynchrony domains in a lattice of coupled oscillators. After a reformulation in terms of a local order parameter, the problem can be reduced to partial differential equations. We find uniformly rotating, spatially periodic chimera patterns as solutions of a reversible ordinary differential equation, and demonstrate a plethora of such states. In the limit of neutral coupling they reduce to analytical solutions in the form of one- and two-point chimera patterns as well as localized chimera solitons. Patterns at weakly attracting coupling are characterized by virtue of a perturbative approach. Stability analysis reveals that only the simplest chimeras with one synchronous region are stable.

Microscopical and elemental FESEM and Phenom ProX-SEM-EDS analysis of osteocyte- and blood vessel-like microstructures obtained from fossil vertebrates of the Eocene Messel Pit, Germany.

PubMed

Cadena, Edwin

2016-01-01

The Eocene (∾48 Ma) Messel Pit in Germany is a UNESCO World Heritage Site because of its exceptionally preserved fossils, including vertebrates, invertebrates, and plants. Messel fossil vertebrates are typically characterized by their articulated state, and in some cases the skin, hair, feathers, scales and stomach contents are also preserved. Despite the exceptional macroscopic preservation of Messel fossil vertebrates, the microstructural aspect of these fossils has been poorly explored. In particular, soft tissue structures such as hair or feathers have not been chemically analyzed, nor have bone microstructures. I report here the preservation and recovery of osteocyte-like and blood vessel-like microstructures from the bone of Messel Pit specimens, including the turtles Allaeochelys crassesculpta and Neochelys franzeni, the crocodile Diplocynodon darwini, and the pangolin Eomanis krebsi. I used a Field Emission Scanning Electron Microscope (FESEM) and a Phenom ProX desktop scanning electron microscope (LOT-QuantumDesign) equipped with a thermionic CeB6 source and a high sensitivity multi-mode backscatter electron (BSE) for microscopical and elemental characterization of these bone microstructures. Osteocyte-like and blood vessel-like microstructures are constituted by a thin layer (∾50 nm thickness), external and internal mottled texture with slightly marked striations. Circular to linear marks are common on the external surface of the osteocyte-like microstructures and are interpreted as microbial troughs. Iron (Fe) is the most abundant element found in the osteocyte-like and blood vessel-like microstructures, but not in the bone matrix or collagen fibril-like microstructures. The occurrence of well-preserved soft-tissue elements (at least their physical form) establishes a promising background for future studies on preservation of biomolecules (proteins or DNA) in Messel Pit fossils.

Lennox-Gastaut syndrome of unknown cause: phenotypic characteristics of patients in the Epilepsy Phenome/Genome Project.

PubMed

Widdess-Walsh, Peter; Dlugos, Dennis; Fahlstrom, Robyn; Joshi, Sucheta; Shellhaas, Renée; Boro, Alex; Sullivan, Joseph; Geller, Eric

2013-11-01

Lennox-Gastaut syndrome (LGS) is a devastating childhood-onset epilepsy syndrome. The cause is unknown in 25% of cases. Little has been described about the specific clinical or electroencephalography (EEG) features of LGS of unknown or genetic cause (LGS(u)). The Epilepsy Phenome/Genome Project (EPGP) aims to characterize LGS(u) by phenotypic analysis of patients with LGS(u) and their parents. One hundred thirty-five patients with LGS with no known etiology and their parents were enrolled from 19 EPGP centers in the United States and Australia. Clinical data from medical records, standardized questionnaires, imaging, and EEG were collected with use of online informatics systems developed for EPGP. LGS(u) in the EPGP cohort had a broad range of onset of epilepsy from 1 to 13 years, was male predominant (p < 0.0002), and was associated with normal development prior to seizure onset in 59.2% of patients. Despite the diagnosis, almost half of the adult patients with LGS(u) completed secondary school. Parents were cognitively normal. All subjects had EEG recordings with generalized epileptiform abnormalities with a spike wave frequency range of 1-5 Hz (median 2 Hz), whereas 8.1% of subjects had EEG studies with a normal posterior dominant rhythm. Almost 12% of patients evolved from West syndrome. LGS(u) has distinctive characteristics including a broad age range of onset, male predominance, and often normal development prior to the onset of seizures. Cognitive achievements such as completion of secondary school were possible in half of adult patients. Our phenotypic description of LGS(u) coupled with future genetic studies will advance our understanding of this epilepsy syndrome. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Advanced phenotyping and phenotype data analysis for the study of plant growth and development.

PubMed

Rahaman, Md Matiur; Chen, Dijun; Gillani, Zeeshan; Klukas, Christian; Chen, Ming

2015-01-01

Due to an increase in the consumption of food, feed, fuel and to meet global food security needs for the rapidly growing human population, there is a necessity to breed high yielding crops that can adapt to the future climate changes, particularly in developing countries. To solve these global challenges, novel approaches are required to identify quantitative phenotypes and to explain the genetic basis of agriculturally important traits. These advances will facilitate the screening of germplasm with high performance characteristics in resource-limited environments. Recently, plant phenomics has offered and integrated a suite of new technologies, and we are on a path to improve the description of complex plant phenotypes. High-throughput phenotyping platforms have also been developed that capture phenotype data from plants in a non-destructive manner. In this review, we discuss recent developments of high-throughput plant phenotyping infrastructure including imaging techniques and corresponding principles for phenotype data analysis.

The First Organ-Based Ontology for Arthropods (Ontology of Arthropod Circulatory Systems - OArCS) and its Integration into a Novel Formalization Scheme for Morphological Descriptions.

PubMed

Wirkner, Christian S; Göpel, Torben; Runge, Jens; Keiler, Jonas; Klussmann-Fricke, Bastian-Jesper; Huckstorf, Katarina; Scholz, Stephan; Mikó, István; J Yoder, Matthew; Richter, Stefan

2017-09-01

Morphology, the oldest discipline in the biosciences, is currently experiencing a renaissance in the field of comparative phenomics. However, morphological/phenotypic research still suffers on various levels from a lack of standards. This shortcoming, first highlighted as the "linguistic problem of morphology", concerns the usage of terminology and also the need for formalization of morphological descriptions themselves, something of paramount importance not only to the field of morphology but also when it comes to the use of phenotypic data in systematics and evolutionary biology. We therefore argue, that for morphological descriptions, the basis of all systematic and evolutionary interpretations, ontologies need to be utilized which are based exclusively on structural qualities/properties and which in no case include statements about homology and/or function. Statements about homology and function constitute interpretations on a different or higher level. Based on these "anatomy ontologies", further ontological dimensions (e.g., referring to functional properties or homology) may be exerted for a broad use in evolutionary phenomics. To this end we present the first organ-based ontology for the most species-rich animal group, the Arthropoda. Our Ontology of Arthropod Circulatory Systems (OArCS) contains a comprehensive collection of 383 terms (i.e., labels) tied to 296 concepts (i.e., definitions) collected from the literature on phenotypic aspects of circulatory organ features in arthropods. All of the concepts used in OArCS are based exclusively on structural features, and in the context of the ontology are independent of homology and functional assumptions. We cannot rule out that in some cases, terms are used which in traditional usage and previous accounts might have implied homology and/or function (e.g. heart, sternal artery). Concepts are composed of descriptive elements that are used to classify observed instances into the organizational framework of the ontology. That is, descriptions in ontologies are only descriptions of individuals if they are necessary/and or sufficient representations of attributes (independently) observed and recorded for an individual. In addition, we here present for the first time an entirely new approach to formalizing phenotypic research, a semantic model for the description of a complex organ system in a highly disparate taxon, the arthropods. We demonstrate this with a formalized morphological description of the hemolymph vascular system in one specimen of the European garden spider Araneus diadematus. Our description targets five categories of descriptive statement: "position", "spatial relationships", "shape", "constituents", and "connections", as the corresponding formalizations constitute exemplary patterns useful not only when talking about the circulatory system, but also in descriptions in general. The downstream applications of computer-parsable morphological descriptions are widespread, with their core utility being the fact that they make it possible to compare collective description sets in computational time, that is, very quickly. Among other things, this facilitates the identification of phenotypic plasticity and variation when single individuals are compared, the identification of those traits which correlate between and within taxa, and the identification of links between morphological traits and genetic (using GO, Gene Ontology) or environmental (using ENVO, Environmental Ontology) factors. [Arthropoda; concept; function; hemolymph vascular system; homology; terminology.]. © The Author(s) 2017. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A simple model for pollen-parent fecundity distributions in bee-pollinated forage legume polycrosses

USDA-ARS?s Scientific Manuscript database

Random mating or panmixis is a fundamental assumption in quantitative genetic theory. Random mating is sometimes thought to occur in actual fact although a large body of empirical work shows that this is often not the case in nature. Models have been developed to model many non-random mating phenome...

The Planteome database: an integrated resource for reference ontologies, plant genomics and phenomics

PubMed Central

Cooper, Laurel; Meier, Austin; Laporte, Marie-Angélique; Elser, Justin L; Mungall, Chris; Sinn, Brandon T; Cavaliere, Dario; Carbon, Seth; Dunn, Nathan A; Smith, Barry; Qu, Botong; Preece, Justin; Zhang, Eugene; Todorovic, Sinisa; Gkoutos, Georgios; Doonan, John H; Stevenson, Dennis W; Arnaud, Elizabeth

2018-01-01

Abstract The Planteome project (http://www.planteome.org) provides a suite of reference and species-specific ontologies for plants and annotations to genes and phenotypes. Ontologies serve as common standards for semantic integration of a large and growing corpus of plant genomics, phenomics and genetics data. The reference ontologies include the Plant Ontology, Plant Trait Ontology and the Plant Experimental Conditions Ontology developed by the Planteome project, along with the Gene Ontology, Chemical Entities of Biological Interest, Phenotype and Attribute Ontology, and others. The project also provides access to species-specific Crop Ontologies developed by various plant breeding and research communities from around the world. We provide integrated data on plant traits, phenotypes, and gene function and expression from 95 plant taxa, annotated with reference ontology terms. The Planteome project is developing a plant gene annotation platform; Planteome Noctua, to facilitate community engagement. All the Planteome ontologies are publicly available and are maintained at the Planteome GitHub site (https://github.com/Planteome) for sharing, tracking revisions and new requests. The annotated data are freely accessible from the ontology browser (http://browser.planteome.org/amigo) and our data repository. PMID:29186578

Surpassing the Target: How a Recruitment Campaign Transformed the Participant Accrual Trajectory in the Epilepsy Phenome/Genome Project.

PubMed

McGovern, Kathleen; Karn, Catharine Freyer; Fox, Kristen

2015-10-01

Participant recruitment challenges pervade the majority of publicly funded clinical trials. However, little is known about methods for enhancing participant accrual. The Epilepsy Phenome/Genome Project (EPGP), a multicenter study funded by the National Institute of Neurological Disorders and Stroke (NINDS), aimed to enroll a total of 5,250 participants to better understand the genetic causes and phenotypic manifestations of epilepsy. However, similar to other trials, EPGP encountered recruitment challenges, and by the end of its first year, net enrollment was only 48% of the target for that time. To address this, EPGP established a National Participant Recruitment Campaign and began implementing and tracking the enrollment outcomes of a variety of proven and relatively novel recruitment methods. At the conclusion of the project, EPGP had successfully enrolled a total of 5,445 participants, thus surpassing its enrollment target. Data pertaining to EPGP's National Participant Recruitment Campaign was analyzed retrospectively, and the results are reported here, so that other multicenter trials may consider these methods in their recruitment planning and potentially avoid the costly repercussions of participant accrual issues. © 2015 Wiley Periodicals, Inc.

Getting Ready for the Human Phenome Project: The 2012 Forum of the Human Variome Project

PubMed Central

Oetting, William S.; Robinson, Peter N.; Greenblatt, Marc S.; Cotton, Richard G.; Beck, Tim; Carey, John C.; Doelken, Sandra C.; Girdea, Marta; Groza, Tudor; Hamilton, Carol M.; Hamosh, Ada; Kerner, Berit; MacArthur, Jacqueline A. L.; Maglott, Donna R.; Mons, Barend; Rehm, Heidi L.; Schofield, Paul N.; Searle, Beverly A.; Smedley, Damian; Smith, Cynthia L.; Bernstein, Inge Thomsen; Zankl, Andreas; Zhao, Eric Y.

2014-01-01

A forum of the Human Variome Project (HVP) was held as a satellite to the 2012 Annual Meeting of the American Society of Human Genetics in San Francisco, California. The theme of this meeting was “Getting Ready for the Human Phenome Project.” Understanding the genetic contribution to both rare single-gene “Mendelian” disorders and more complex common diseases will require integration of research efforts among many fields and better defined phenotypes. The HVP is dedicated to bringing together researchers and research populations throughout the world to provide the resources to investigate the impact of genetic variation on disease. To this end, there needs to be a greater sharing of phenotype and genotype data. For this to occur, many databases that currently exist will need to become interoperable to allow for the combining of cohorts with similar phenotypes to increase statistical power for studies attempting to identify novel disease genes or causative genetic variants. Improved systems and tools that enhance the collection of phenotype data from clinicians are urgently needed. This meeting begins the HVP’s effort toward this important goal. PMID:23401191

Fostering synergy between cell biology and systems biology.

PubMed

Eddy, James A; Funk, Cory C; Price, Nathan D

2015-08-01

In the shared pursuit of elucidating detailed mechanisms of cell function, systems biology presents a natural complement to ongoing efforts in cell biology. Systems biology aims to characterize biological systems through integrated and quantitative modeling of cellular information. The process of model building and analysis provides value through synthesizing and cataloging information about cells and molecules, predicting mechanisms and identifying generalizable themes, generating hypotheses and guiding experimental design, and highlighting knowledge gaps and refining understanding. In turn, incorporating domain expertise and experimental data is crucial for building towards whole cell models. An iterative cycle of interaction between cell and systems biologists advances the goals of both fields and establishes a framework for mechanistic understanding of the genome-to-phenome relationship. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Phenome-genome association studies of pancreatic cancer: new targets for therapy and diagnosis.

PubMed

Narayanan, Ramaswamy

2015-01-01

Pancreatic cancer, has a very high mortality rate and requires novel molecular targets for diagnosis and therapy. Genetic association studies over databases offer an attractive starting point for gene discovery. The National Center for Biotechnology Information (NCBI) Phenome Genome Integrator (PheGenI) tool was enriched for pancreatic cancer-associated traits. The genes associated with the trait were characterized using diverse bioinformatics tools for Genome-Wide Association (GWA), transcriptome and proteome profile and protein classes for motif and domain. Two hundred twenty-six genes were identified that had a genetic association with pancreatic cancer in the human genome. This included 25 uncharacterized open reading frames (ORFs). Bioinformatics analysis of these ORFs identified putative druggable proteins and biomarkers including enzymes, transporters and G-protein-coupled receptor signaling proteins. Secreted proteins including a neuroendocrine factor and a chemokine were identified. Five out of these ORFs encompassed non coding RNAs. The ORF protein expression was detected in numerous body fluids, such as ascites, bile, pancreatic juice, milk, plasma, serum and saliva. Transcriptome and proteome analyses showed a correlation of mRNA and protein expression for nine ORFs. Analysis of the Catalogue of Somatic Mutations in Cancer (COSMIC) database revealed a strong correlation across copy number variations and mRNA over-expression for four ORFs. Mining of the International Cancer Gene Consortium (ICGC) database identified somatic mutations in a significant number of pancreatic patients' tumors for most of these ORFs. The pancreatic cancer-associated ORFs were also found to be genetically associated with other neoplasms, including leukemia, malignant melanoma, neuroblastoma and prostate carcinomas, as well as other unrelated diseases and disorders, such as Alzheimer's disease, Crohn's disease, coronary diseases, attention deficit disorder and addiction. Based on Genome-Wide Association Studies (GWAS), copy number variations, somatic mutational status and correlation of gene expression in pancreatic tumors at the mRNA and protein level, expression specificity in normal tissues and detection in body fluids, six ORFs emerged as putative leads for pancreatic cancer. These six targets provide a basis for accelerated drug discovery and diagnostic marker development for pancreatic cancer. Copyright© 2015, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

Genetic resources offer efficient tools for rice functional genomics research.

PubMed

Lo, Shuen-Fang; Fan, Ming-Jen; Hsing, Yue-Ie; Chen, Liang-Jwu; Chen, Shu; Wen, Ien-Chie; Liu, Yi-Lun; Chen, Ku-Ting; Jiang, Mirng-Jier; Lin, Ming-Kuang; Rao, Meng-Yen; Yu, Lin-Chih; Ho, Tuan-Hua David; Yu, Su-May

2016-05-01

Rice is an important crop and major model plant for monocot functional genomics studies. With the establishment of various genetic resources for rice genomics, the next challenge is to systematically assign functions to predicted genes in the rice genome. Compared with the robustness of genome sequencing and bioinformatics techniques, progress in understanding the function of rice genes has lagged, hampering the utilization of rice genes for cereal crop improvement. The use of transfer DNA (T-DNA) insertional mutagenesis offers the advantage of uniform distribution throughout the rice genome, but preferentially in gene-rich regions, resulting in direct gene knockout or activation of genes within 20-30 kb up- and downstream of the T-DNA insertion site and high gene tagging efficiency. Here, we summarize the recent progress in functional genomics using the T-DNA-tagged rice mutant population. We also discuss important features of T-DNA activation- and knockout-tagging and promoter-trapping of the rice genome in relation to mutant and candidate gene characterizations and how to more efficiently utilize rice mutant populations and datasets for high-throughput functional genomics and phenomics studies by forward and reverse genetics approaches. These studies may facilitate the translation of rice functional genomics research to improvements of rice and other cereal crops. © 2015 John Wiley & Sons Ltd.

Fifteen years of quantitative trait loci studies in fish: challenges and future directions.

PubMed

Ashton, David T; Ritchie, Peter A; Wellenreuther, Maren

2017-03-01

Understanding the genetic basis of phenotypic variation is a major challenge in biology. Here, we systematically evaluate 146 quantitative trait loci (QTL) studies on teleost fish over the last 15 years to investigate (i) temporal trends and (ii) factors affecting QTL detection and fine-mapping. The number of fish QTL studies per year increased over the review period and identified a cumulative number of 3632 putative QTLs. Most studies used linkage-based mapping approaches and were conducted on nonmodel species with limited genomic resources. A gradual and moderate increase in the size of the mapping population and a sharp increase in marker density from 2011 onwards were observed; however, the number of QTLs and variance explained by QTLs changed only minimally over the review period. Based on these findings, we discuss the causative factors and outline how larger sample sizes, phenomics, comparative genomics, epigenetics and software development could improve both the quantity and quality of QTLs in future genotype-phenotype studies. Given that the technical limitations on DNA sequencing have mostly been overcome in recent years, a renewed focus on these and other study design factors will likely lead to significant improvements in QTL studies in the future. © 2016 John Wiley & Sons Ltd.

World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project: IV. Tissue collection, processing, and storage in endometriosis research

PubMed Central

Fassbender, Amelie; Rahmioglu, Nilufer; Vitonis, Allison F.; Viganò, Paola; Giudice, Linda C.; D’Hooghe, Thomas M.; Hummelshoj, Lone; Adamson, G. David; Becker, Christian M.; Missmer, Stacey A.; Zondervan, Krina T.; Adamson, G.D.; Allaire, C.; Anchan, R.; Becker, C.M.; Bedaiwy, M.A.; Buck Louis, G.M.; Calhaz-Jorge, C.; Chwalisz, K.; D'Hooghe, T.M.; Fassbender, A.; Faustmann, T.; Fazleabas, A.T.; Flores, I.; Forman, A.; Fraser, I.; Giudice, L.C.; Gotte, M.; Gregersen, P.; Guo, S.-W.; Harada, T.; Hartwell, D.; Horne, A.W.; Hull, M.L.; Hummelshoj, L.; Ibrahim, M.G.; Kiesel, L.; Laufer, M.R.; Machens, K.; Mechsner, S.; Missmer, S.A.; Montgomery, G.W.; Nap, A.; Nyegaard, M.; Osteen, K.G.; Petta, C.A.; Rahmioglu, N.; Renner, S.P.; Riedlinger, J.; Roehrich, S.; Rogers, P.A.; Rombauts, L.; Salumets, A.; Saridogan, E.; Seckin, T.; Stratton, P.; Sharpe-Timms, K.L.; Tworoger, S.; Vigano, P.; Vincent, K.; Vitonis, A.F.; Wienhues-Thelen, U.-H.; Yeung, P.P.; Yong, P.; Zondervan, K.T.

2014-01-01

Objective To harmonize standard operating procedures (SOPs) and standardize the recording of associated data for collection, processing, and storage of human tissues relevant to endometriosis. Design An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries on five continents. Setting In 2013, two workshops were conducted followed by global consultation, bringing together 54 leaders in endometriosis research and sample processing from around the world. Patient(s) None. Intervention(s) Consensus SOPs were based on: 1) systematic comparison of SOPs from 24 global centers collecting tissue samples from women with and without endometriosis on a medium or large scale (publication on >100 cases); 2) literature evidence where available, or consultation with laboratory experts otherwise; and 3) several global consultation rounds. Main Outcome Measure(s) Standard recommended and minimum required SOPs for tissue collection, processing, and storage in endometriosis research. Result(s) We developed “recommended standard” and “minimum required” SOPs for the collection, processing, and storage of ectopic and eutopic endometrium, peritoneum, and myometrium, and a biospecimen data collection form necessary for interpretation of sample-derived results. Conclusion(s) The EPHect SOPs allow endometriosis research centers to decrease variability in tissue-based results, facilitating between-center comparisons and collaborations. The procedures are also relevant to research into other gynecologic conditions involving endometrium, myometrium, and peritoneum. The consensus SOPs are based on the best available evidence; areas with limited evidence are identified as requiring further pilot studies. The SOPs will be reviewed based on investigator feedback and through systematic triannual follow-up. Updated versions will be made available at: http://endometriosisfoundation.org/ephect. PMID:25256928

Advanced phenotyping and phenotype data analysis for the study of plant growth and development

PubMed Central

Rahaman, Md. Matiur; Chen, Dijun; Gillani, Zeeshan; Klukas, Christian; Chen, Ming

2015-01-01

Due to an increase in the consumption of food, feed, fuel and to meet global food security needs for the rapidly growing human population, there is a necessity to breed high yielding crops that can adapt to the future climate changes, particularly in developing countries. To solve these global challenges, novel approaches are required to identify quantitative phenotypes and to explain the genetic basis of agriculturally important traits. These advances will facilitate the screening of germplasm with high performance characteristics in resource-limited environments. Recently, plant phenomics has offered and integrated a suite of new technologies, and we are on a path to improve the description of complex plant phenotypes. High-throughput phenotyping platforms have also been developed that capture phenotype data from plants in a non-destructive manner. In this review, we discuss recent developments of high-throughput plant phenotyping infrastructure including imaging techniques and corresponding principles for phenotype data analysis. PMID:26322060

[Methods of high-throughput plant phenotyping for large-scale breeding and genetic experiments].

PubMed

Afonnikov, D A; Genaev, M A; Doroshkov, A V; Komyshev, E G; Pshenichnikova, T A

2016-07-01

Phenomics is a field of science at the junction of biology and informatics which solves the problems of rapid, accurate estimation of the plant phenotype; it was rapidly developed because of the need to analyze phenotypic characteristics in large scale genetic and breeding experiments in plants. It is based on using the methods of computer image analysis and integration of biological data. Owing to automation, new approaches make it possible to considerably accelerate the process of estimating the characteristics of a phenotype, to increase its accuracy, and to remove a subjectivism (inherent to humans). The main technologies of high-throughput plant phenotyping in both controlled and field conditions, their advantages and disadvantages, and also the prospects of their use for the efficient solution of problems of plant genetics and breeding are presented in the review.

Environmental Biotechnology: Moving from the Flask to the Field

DTIC Science & Technology

1991-09-30

biosorption , Biosorption of metal ions is a phenome- non exhibited by both alive and dead microbial cells. The detailed investigation of the mechanism of... biosorption has revealed that biosorption is a physical-chemical process whereby selected areas of the microbial cell exhibit high selectivity and...dead cells than by the same cells alive. The use of proper chemical solutions (eluants) is capable of reversing the equilibrium of biosorption

Generating series for GUE correlators

NASA Astrophysics Data System (ADS)

Dubrovin, Boris; Yang, Di

2017-11-01

We extend to the Toda lattice hierarchy the approach of Bertola et al. (Phys D Nonlinear Phenom 327:30-57, 2016; IMRN, 2016) to computation of logarithmic derivatives of tau-functions in terms of the so-called matrix resolvents of the corresponding difference Lax operator. As a particular application we obtain explicit generating series for connected GUE correlators. On this basis an efficient recursive procedure for computing the correlators in full genera is developed.

Patterns of genomic and phenomic diversity in wine and table grapes

PubMed Central

Migicovsky, Zoë; Sawler, Jason; Gardner, Kyle M; Aradhya, Mallikarjuna K; Prins, Bernard H; Schwaninger, Heidi R; Bustamante, Carlos D; Buckler, Edward S; Zhong, Gan-Yuan; Brown, Patrick J; Myles, Sean

2017-01-01

Grapes are one of the most economically and culturally important crops worldwide, and they have been bred for both winemaking and fresh consumption. Here we evaluate patterns of diversity across 33 phenotypes collected over a 17-year period from 580 table and wine grape accessions that belong to one of the world’s largest grape gene banks, the grape germplasm collection of the United States Department of Agriculture. We find that phenological events throughout the growing season are correlated, and quantify the marked difference in size between table and wine grapes. By pairing publicly available historical phenotype data with genome-wide polymorphism data, we identify large effect loci controlling traits that have been targeted during domestication and breeding, including hermaphroditism, lighter skin pigmentation and muscat aroma. Breeding for larger berries in table grapes was traditionally concentrated in geographic regions where Islam predominates and alcohol was prohibited, whereas wine grapes retained the ancestral smaller size that is more desirable for winemaking in predominantly Christian regions. We uncover a novel locus with a suggestive association with berry size that harbors a signature of positive selection for larger berries. Our results suggest that religious rules concerning alcohol consumption have had a marked impact on patterns of phenomic and genomic diversity in grapes. PMID:28791127

Patterns of genomic and phenomic diversity in wine and table grapes.

PubMed

Migicovsky, Zoë; Sawler, Jason; Gardner, Kyle M; Aradhya, Mallikarjuna K; Prins, Bernard H; Schwaninger, Heidi R; Bustamante, Carlos D; Buckler, Edward S; Zhong, Gan-Yuan; Brown, Patrick J; Myles, Sean

2017-01-01

Grapes are one of the most economically and culturally important crops worldwide, and they have been bred for both winemaking and fresh consumption. Here we evaluate patterns of diversity across 33 phenotypes collected over a 17-year period from 580 table and wine grape accessions that belong to one of the world's largest grape gene banks, the grape germplasm collection of the United States Department of Agriculture. We find that phenological events throughout the growing season are correlated, and quantify the marked difference in size between table and wine grapes. By pairing publicly available historical phenotype data with genome-wide polymorphism data, we identify large effect loci controlling traits that have been targeted during domestication and breeding, including hermaphroditism, lighter skin pigmentation and muscat aroma. Breeding for larger berries in table grapes was traditionally concentrated in geographic regions where Islam predominates and alcohol was prohibited, whereas wine grapes retained the ancestral smaller size that is more desirable for winemaking in predominantly Christian regions. We uncover a novel locus with a suggestive association with berry size that harbors a signature of positive selection for larger berries. Our results suggest that religious rules concerning alcohol consumption have had a marked impact on patterns of phenomic and genomic diversity in grapes.

Constructing Adverse Outcome Pathways: a Demonstration of ...

EPA Pesticide Factsheets

Adverse outcome pathway (AOP) provides a conceptual framework to evaluate and integrate chemical toxicity and its effects across the levels of biological organization. As such, it is essential to develop a resource-efficient and effective approach to extend molecular initiating events (MIEs) of chemicals to their downstream phenotypes of a greater regulatory relevance. A number of ongoing public phenomics (high throughput phenotyping) efforts have been generating abundant phenotypic data annotated with ontology terms. These phenotypes can be analyzed semantically and linked to MIEs of interest, all in the context of a knowledge base integrated from a variety of ontologies for various species and knowledge domains. In such analyses, two phenotypic profiles (PPs; anchored by genes or diseases) each characterized by multiple ontology terms are compared for their semantic similarities within a common ontology graph, but across boundaries of species and knowledge domains. Taking advantage of publicly available ontologies and software tool kits, we have implemented an OS-Mapping (Ontology-based Semantics Mapping) approach as a Java application, and constructed a network of 19383 PPs as nodes with edges weighed by their pairwise semantic similarity scores. Individual PPs were assembled from public phenomics data. Out of possible 1.87×108 pairwise connections among these nodes, about 71% of them have similarity scores between 0.2 and the maximum possible of 1.0.

Worldwide Survey of Substance Abuse and Health Behaviors among Military Personnel (1988)

DTIC Science & Technology

1989-01-25

military medical per- sonnel. * Almost 40 percent of military personnel report having changed their sexual behavior because of concern about getting...through a comprehensive system of medical care. A concen- trated health promotion program, however, has been a fairly recent phenome- non. In 1986, the...the prevalence of substance use (alcohol use, non- medical drug use, tobacco use) among military personnel, " identify the physical, social and work

Quantitative monitoring of Arabidopsis thaliana growth and development using high-throughput plant phenotyping

PubMed Central

Arend, Daniel; Lange, Matthias; Pape, Jean-Michel; Weigelt-Fischer, Kathleen; Arana-Ceballos, Fernando; Mücke, Ingo; Klukas, Christian; Altmann, Thomas; Scholz, Uwe; Junker, Astrid

2016-01-01

With the implementation of novel automated, high throughput methods and facilities in the last years, plant phenomics has developed into a highly interdisciplinary research domain integrating biology, engineering and bioinformatics. Here we present a dataset of a non-invasive high throughput plant phenotyping experiment, which uses image- and image analysis- based approaches to monitor the growth and development of 484 Arabidopsis thaliana plants (thale cress). The result is a comprehensive dataset of images and extracted phenotypical features. Such datasets require detailed documentation, standardized description of experimental metadata as well as sustainable data storage and publication in order to ensure the reproducibility of experiments, data reuse and comparability among the scientific community. Therefore the here presented dataset has been annotated using the standardized ISA-Tab format and considering the recently published recommendations for the semantical description of plant phenotyping experiments. PMID:27529152

Quantitative monitoring of Arabidopsis thaliana growth and development using high-throughput plant phenotyping.

PubMed

Arend, Daniel; Lange, Matthias; Pape, Jean-Michel; Weigelt-Fischer, Kathleen; Arana-Ceballos, Fernando; Mücke, Ingo; Klukas, Christian; Altmann, Thomas; Scholz, Uwe; Junker, Astrid

2016-08-16

With the implementation of novel automated, high throughput methods and facilities in the last years, plant phenomics has developed into a highly interdisciplinary research domain integrating biology, engineering and bioinformatics. Here we present a dataset of a non-invasive high throughput plant phenotyping experiment, which uses image- and image analysis- based approaches to monitor the growth and development of 484 Arabidopsis thaliana plants (thale cress). The result is a comprehensive dataset of images and extracted phenotypical features. Such datasets require detailed documentation, standardized description of experimental metadata as well as sustainable data storage and publication in order to ensure the reproducibility of experiments, data reuse and comparability among the scientific community. Therefore the here presented dataset has been annotated using the standardized ISA-Tab format and considering the recently published recommendations for the semantical description of plant phenotyping experiments.

Rcupcake: an R package for querying and analyzing biomedical data through the BD2K PIC-SURE RESTful API.

PubMed

Gutiérrez-Sacristán, Alba; Guedj, Romain; Korodi, Gabor; Stedman, Jason; Furlong, Laura I; Patel, Chirag J; Kohane, Isaac S; Avillach, Paul

2018-04-15

In the era of big data and precision medicine, the number of databases containing clinical, environmental, self-reported and biochemical variables is increasing exponentially. Enabling the experts to focus on their research questions rather than on computational data management, access and analysis is one of the most significant challenges nowadays. We present Rcupcake, an R package that contains a variety of functions for leveraging different databases through the BD2K PIC-SURE RESTful API and facilitating its query, analysis and interpretation. The package offers a variety of analysis and visualization tools, including the study of the phenotype co-occurrence and prevalence, according to multiple layers of data, such as phenome, exposome or genome. The package is implemented in R and is available under Mozilla v2 license from GitHub (https://github.com/hms-dbmi/Rcupcake). Two reproducible case studies are also available (https://github.com/hms-dbmi/Rcupcake-case-studies/blob/master/SSCcaseStudy_v01.ipynb, https://github.com/hms-dbmi/Rcupcake-case-studies/blob/master/NHANEScaseStudy_v01.ipynb). paul_avillach@hms.harvard.edu. Supplementary data are available at Bioinformatics online.

Exome capture sequencing reveals new insights into hepatitis B virus-induced hepatocellular carcinoma at the early stage of tumorigenesis.

PubMed

Chen, Yong; Wang, Lijuan; Xu, Hexiang; Liu, Xingxiang; Zhao, Yingren

2013-10-01

Hepatocellular carcinoma (HCC), the most common type of liver cancer, is the third primary cause of cancer-related mortality worldwide. The molecular mechanisms underlying the initiation and formation of HCC remain obscure. In the present study, we performed exome sequencing using tumor and normal tissues from 3 hepatitis B virus (HBV)-positive BCLC stage A HCC patients. Bioinformatic analysis was performed to find candidate protein-altering somatic mutations. Eighty damaging mutations were validated and 59 genes were reported to be mutated in HBV-related HCCs for the first time here. Further analysis using whole genome sequencing (WGS) data of 88 HBV-related HCC patients from the European Genome-phenome Archive database showed that mutations in 33 of the 59 genes were also detected in other samples. Variants of two newly found genes, ZNF717 and PARP4, were detected in more than 10% of the WGS samples. Several other genes, such as FLNA and CNTN2, are also noteworthy. Thus, the exome sequencing analysis of three BCLC stage A patients provides new insights into the molecular events governing the early steps of HBV-induced HCC tumorigenesis.

Comments on the Voigt function implementation in the Astropy and SpectraPlot.com packages

NASA Astrophysics Data System (ADS)

Schreier, Franz

2018-07-01

The Voigt profile is important for spectroscopy, astrophysics, and many other fields of physics, but is notoriously difficult to compute. McLean et al. [1] [J. Electron Spectrosc. & Relat. Phenom., 1994] have proposed an approximation using a sum of Lorentzians. Our assessment indicates that this algorithm has significant errors for small arguments. After a brief survey of the requirements for spectroscopy we give a short list of both efficient and accurate codes and recommend implementations based on rational approximations.

Transcriptome complexity in cardiac development and diseases--an expanding universe between genome and phenome.

PubMed

Gao, Chen; Wang, Yibin

2014-01-01

With the advancement of transcriptome profiling by micro-arrays and high-throughput RNA-sequencing, transcriptome complexity and its dynamics are revealed at different levels in cardiovascular development and diseases. In this review, we will highlight the recent progress in our knowledge of cardiovascular transcriptome complexity contributed by RNA splicing, RNA editing and noncoding RNAs. The emerging importance of many of these previously under-explored aspects of gene regulation in cardiovascular development and pathology will be discussed.

Synchrotron microCT imaging of soft tissue in juvenile zebrafish reveals retinotectal projections

NASA Astrophysics Data System (ADS)

Xin, Xuying; Clark, Darin; Ang, Khai Chung; van Rossum, Damian B.; Copper, Jean; Xiao, Xianghui; La Riviere, Patrick J.; Cheng, Keith C.

2017-02-01

Biomedical research and clinical diagnosis would benefit greatly from full volume determinations of anatomical phenotype. Comprehensive tools for morphological phenotyping are central for the emerging field of phenomics, which requires high-throughput, systematic, accurate, and reproducible data collection from organisms affected by genetic, disease, or environmental variables. Theoretically, complete anatomical phenotyping requires the assessment of every cell type in the whole organism, but this ideal is presently untenable due to the lack of an unbiased 3D imaging method that allows histopathological assessment of any cell type despite optical opacity. Histopathology, the current clinical standard for diagnostic phenotyping, involves the microscopic study of tissue sections to assess qualitative aspects of tissue architecture, disease mechanisms, and physiological state. However, quantitative features of tissue architecture such as cellular composition and cell counting in tissue volumes can only be approximated due to characteristics of tissue sectioning, including incomplete sampling and the constraints of 2D imaging of 5 micron thick tissue slabs. We have used a small, vertebrate organism, the zebrafish, to test the potential of microCT for systematic macroscopic and microscopic morphological phenotyping. While cell resolution is routinely achieved using methods such as light sheet fluorescence microscopy and optical tomography, these methods do not provide the pancellular perspective characteristic of histology, and are constrained by the limited penetration of visible light through pigmented and opaque specimens, as characterizes zebrafish juveniles. Here, we provide an example of neuroanatomy that can be studied by microCT of stained soft tissue at 1.43 micron isotropic voxel resolution. We conclude that synchrotron microCT is a form of 3D imaging that may potentially be adopted towards more reproducible, large-scale, morphological phenotyping of optically opaque tissues. Further development of soft tissue microCT, visualization and quantitative tool development will enhance its utility.

Phenotyping of Eggplant Wild Relatives and Interspecific Hybrids with Conventional and Phenomics Descriptors Provides Insight for Their Potential Utilization in Breeding

PubMed Central

Kaushik, Prashant; Prohens, Jaime; Vilanova, Santiago; Gramazio, Pietro; Plazas, Mariola

2016-01-01

Eggplant (Solanum melongena) is related to a large number of wild species that are a source of variation for breeding programmes, in particular for traits related to adaptation to climate change. However, wild species remain largely unexploited for eggplant breeding. Detailed phenotypic characterization of wild species and their hybrids with eggplant may allow identifying promising wild species and information on the genetic control and heterosis of relevant traits. We characterizated six eggplant accessions, 21 accessions of 12 wild species (the only primary genepool species S. insanum and 11 secondary genepool species) and 45 interspecific hybrids of eggplant with wild species (18 with S. insanum and 27 with secondary genepool species) using 27 conventional morphological descriptors and 20 fruit morphometric descriptors obtained with the phenomics tool Tomato Analyzer. Significant differences were observed among cultivated, wild and interspecific hybrid groups for 18 conventional and 18 Tomato Analyzer descriptors, with hybrids generally having intermediate values. Wild species were generally more variable than cultivated accessions and interspecific hybrids displayed intermediate ranges of variation and coefficient of variation (CV) values, except for fruit shape traits in which the latter were the most variable. The multivariate principal components analysis (PCA) reveals a clear separation of wild species and cultivated accessions. Interspecific hybrids with S. insanum plotted closer to cultivated eggplant, while hybrids with secondary genepool species generally clustered together with wild species. Many differences were observed among wild species for traits of agronomic interest, which allowed identifying species of greatest potential interest for eggplant breeding. Heterosis values were positive for most vigor-related traits, while for fruit size values were close to zero for hybrids with S. incanum and highly negative for hybrids with secondary genepool species. Our results allowed the identification of potentially interesting wild species and interspecific hybrids for introgression breeding in eggplant. This is an important step for broadening the genetic base of eggplant and for breeding for adaptation to climate change in this crop. PMID:27242876

The epilepsy phenome/genome project.

PubMed

Abou-Khalil, Bassel; Alldredge, Brian; Bautista, Jocelyn; Berkovic, Sam; Bluvstein, Judith; Boro, Alex; Cascino, Gregory; Consalvo, Damian; Cristofaro, Sabrina; Crumrine, Patricia; Devinsky, Orrin; Dlugos, Dennis; Epstein, Michael; Fahlstrom, Robyn; Fiol, Miguel; Fountain, Nathan; Fox, Kristen; French, Jacqueline; Freyer Karn, Catharine; Friedman, Daniel; Geller, Eric; Glauser, Tracy; Glynn, Simon; Haas, Kevin; Haut, Sheryl; Hayward, Jean; Helmers, Sandra; Joshi, Sucheta; Kanner, Andres; Kirsch, Heidi; Knowlton, Robert; Kossoff, Eric; Kuperman, Rachel; Kuzniecky, Ruben; Lowenstein, Daniel; McGuire, Shannon; Motika, Paul; Nesbitt, Gerard; Novotny, Edward; Ottman, Ruth; Paolicchi, Juliann; Parent, Jack; Park, Kristen; Poduri, Annapurna; Risch, Neil; Sadleir, Lynette; Scheffer, Ingrid; Shellhaas, Renee; Sherr, Elliott; Shih, Jerry J; Shinnar, Shlomo; Singh, Rani; Sirven, Joseph; Smith, Michael; Sullivan, Joe; Thio, Liu Lin; Venkat, Anu; Vining, Eileen; von Allmen, Gretchen; Weisenberg, Judith; Widdess-Walsh, Peter; Winawer, Melodie

2013-08-01

Epilepsy is a common neurological disorder that affects approximately 50 million people worldwide. Both risk of epilepsy and response to treatment partly depend on genetic factors, and gene identification is a promising approach to target new prediction, treatment, and prevention strategies. However, despite significant progress in the identification of genes causing epilepsy in families with a Mendelian inheritance pattern, there is relatively little known about the genetic factors responsible for common forms of epilepsy and so-called epileptic encephalopathies. Study design The Epilepsy Phenome/Genome Project (EPGP) is a multi-institutional, retrospective phenotype-genotype study designed to gather and analyze detailed phenotypic information and DNA samples on 5250 participants, including probands with specific forms of epilepsy and, in a subset, parents of probands who do not have epilepsy. EPGP is being executed in four phases: study initiation, pilot, study expansion/establishment, and close-out. This article discusses a number of key challenges and solutions encountered during the first three phases of the project, including those related to (1) study initiation and management, (2) recruitment and phenotyping, and (3) data validation. The study has now enrolled 4223 participants. EPGP has demonstrated the value of organizing a large network into cores with specific roles, managed by a strong Administrative Core that utilizes frequent communication and a collaborative model with tools such as study timelines and performance-payment models. The study also highlights the critical importance of an effective informatics system, highly structured recruitment methods, and expert data review.

PhenoPredict: A disease phenome-wide drug repositioning approach towards schizophrenia drug discovery.

PubMed

Xu, Rong; Wang, QuanQiu

2015-08-01

Schizophrenia (SCZ) is a common complex disorder with poorly understood mechanisms and no effective drug treatments. Despite the high prevalence and vast unmet medical need represented by the disease, many drug companies have moved away from the development of drugs for SCZ. Therefore, alternative strategies are needed for the discovery of truly innovative drug treatments for SCZ. Here, we present a disease phenome-driven computational drug repositioning approach for SCZ. We developed a novel drug repositioning system, PhenoPredict, by inferring drug treatments for SCZ from diseases that are phenotypically related to SCZ. The key to PhenoPredict is the availability of a comprehensive drug treatment knowledge base that we recently constructed. PhenoPredict retrieved all 18 FDA-approved SCZ drugs and ranked them highly (recall=1.0, and average ranking of 8.49%). When compared to PREDICT, one of the most comprehensive drug repositioning systems currently available, in novel predictions, PhenoPredict represented clear improvements over PREDICT in Precision-Recall (PR) curves, with a significant 98.8% improvement in the area under curve (AUC) of the PR curves. In addition, we discovered many drug candidates with mechanisms of action fundamentally different from traditional antipsychotics, some of which had published literature evidence indicating their treatment benefits in SCZ patients. In summary, although the fundamental pathophysiological mechanisms of SCZ remain unknown, integrated systems approaches to studying phenotypic connections among diseases may facilitate the discovery of innovative SCZ drugs. Copyright © 2015 Elsevier Inc. All rights reserved.

Consensus on Recording Deep Endometriosis Surgery: the CORDES statement.

PubMed

Vanhie, A; Meuleman, C; Tomassetti, C; Timmerman, D; D'Hoore, A; Wolthuis, A; Van Cleynenbreugel, B; Dancet, E; Van den Broeck, U; Tsaltas, J; Renner, S P; Ebert, A D; Carmona, F; Abbott, J; Stepniewska, A; Taylor, H; Saridogan, E; Mueller, M; Keckstein, J; Pluchino, N; Janik, G; Zupi, E; Minelli, L; Cooper, M; Dunselman, G; Koh, C; Abrao, M S; Chapron, C; D'Hooghe, T

2016-06-01

Which essential items should be recorded before, during and after endometriosis surgery and in clinical outcome based surgical trials in patients with deep endometriosis (DE)? A DE surgical sheet (DESS) was developed for standardized reporting of the surgical treatment of DE and an international expert consensus proposal on relevant items that should be recorded in surgical outcome trials in women with DE. Surgery is an important treatment for symptomatic DE. So far, data have been reported in such a way that comparison of different surgical techniques is impossible. Therefore, we present an international expert proposal for standardized reporting of surgical treatment and surgical outcome trials in women with DE. International expert consensus based on a systematic review of literature. Taking into account recommendations from Consolidated Standards of Reporting Trials (CONSORT), the Innovation Development Exploration Assessment and Long-term Study (IDEAL), the Initiative on Methods, Measurement and Pain Assessment in Clinical trials (IMMPACT) and the World Endometriosis Research Foundation Phenome and Biobanking Harmonisation Project (WERF EPHect), a systematic literature review on surgical treatment of DE was performed and resulted in a proposal for standardized reporting, adapted by contributions from eight members of the multidisciplinary Leuven University Hospitals Endometriosis Care Program, from 18 international experts and from audience feedback during three international meetings. We have developed the DESS to record in detail the surgical procedures for DE, and an international consensus on pre-, intra- and post-operative data that should be recorded in surgical outcome trials on DE. The recommendations in this paper represent a consensus among international experts based on a systematic review of the literature. For several items and recommendations, high-quality RCTs were not available. Further research is needed to validate and evaluate the recommendations presented here. This international expert consensus for standardized reporting of surgical treatment in women with DE, based on a systematic literature review and international consensus, can be used as a guideline to record and report surgical management of patients with DE and as a guideline to design, execute, interpret and compare clinical trials in this patient population. None of the authors received funding for the development of this paper. M.A. reports personal fees and non-financial support from Bayer Pharma outside the submitted work; H.T. reports a grant from Pfizer and personal fees for being on the advisory board of Perrigo, Abbvie, Allergan and SPD. N/A. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Long-term neural and physiological phenotyping of a single human

PubMed Central

Poldrack, Russell A.; Laumann, Timothy O.; Koyejo, Oluwasanmi; Gregory, Brenda; Hover, Ashleigh; Chen, Mei-Yen; Gorgolewski, Krzysztof J.; Luci, Jeffrey; Joo, Sung Jun; Boyd, Ryan L.; Hunicke-Smith, Scott; Simpson, Zack Booth; Caven, Thomas; Sochat, Vanessa; Shine, James M.; Gordon, Evan; Snyder, Abraham Z.; Adeyemo, Babatunde; Petersen, Steven E.; Glahn, David C.; Reese Mckay, D.; Curran, Joanne E.; Göring, Harald H. H.; Carless, Melanie A.; Blangero, John; Dougherty, Robert; Leemans, Alexander; Handwerker, Daniel A.; Frick, Laurie; Marcotte, Edward M.; Mumford, Jeanette A.

2015-01-01

Psychiatric disorders are characterized by major fluctuations in psychological function over the course of weeks and months, but the dynamic characteristics of brain function over this timescale in healthy individuals are unknown. Here, as a proof of concept to address this question, we present the MyConnectome project. An intensive phenome-wide assessment of a single human was performed over a period of 18 months, including functional and structural brain connectivity using magnetic resonance imaging, psychological function and physical health, gene expression and metabolomics. A reproducible analysis workflow is provided, along with open access to the data and an online browser for results. We demonstrate dynamic changes in brain connectivity over the timescales of days to months, and relations between brain connectivity, gene expression and metabolites. This resource can serve as a testbed to study the joint dynamics of human brain and metabolic function over time, an approach that is critical for the development of precision medicine strategies for brain disorders. PMID:26648521

Building a genome analysis pipeline to predict disease risk and prevent disease.

PubMed

Bromberg, Y

2013-11-01

Reduced costs and increased speed and accuracy of sequencing can bring the genome-based evaluation of individual disease risk to the bedside. While past efforts have identified a number of actionable mutations, the bulk of genetic risk remains hidden in sequence data. The biggest challenge facing genomic medicine today is the development of new techniques to predict the specifics of a given human phenome (set of all expressed phenotypes) encoded by each individual variome (full set of genome variants) in the context of the given environment. Numerous tools exist for the computational identification of the functional effects of a single variant. However, the pipelines taking advantage of full genomic, exomic, transcriptomic (and other) sequences have only recently become a reality. This review looks at the building of methodologies for predicting "variome"-defined disease risk. It also discusses some of the challenges for incorporating such a pipeline into everyday medical practice. © 2013. Published by Elsevier Ltd. All rights reserved.

A Journey Through a Leaf: Phenomics Analysis of Leaf Growth in Arabidopsis thaliana

PubMed Central

Vanhaeren, Hannes; Gonzalez, Nathalie; Inzé, Dirk

2015-01-01

In Arabidopsis, leaves contribute to the largest part of the aboveground biomass. In these organs, light is captured and converted into chemical energy, which plants use to grow and complete their life cycle. Leaves emerge as a small pool of cells at the vegetative shoot apical meristem and develop into planar, complex organs through different interconnected cellular events. Over the last decade, numerous phenotyping techniques have been developed to visualize and quantify leaf size and growth, leading to the identification of numerous genes that contribute to the final size of leaves. In this review, we will start at the Arabidopsis rosette level and gradually zoom in from a macroscopic view on leaf growth to a microscopic and molecular view. Along this journey, we describe different techniques that have been key to identify important events during leaf development and discuss approaches that will further help unraveling the complex cellular and molecular mechanisms that underlie leaf growth. PMID:26217168

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanchez, Savannah E.; Cuevas, Daniel A.; Rostron, Jason E.

Current investigations into phage-host interactions are dependent on extrapolating knowledge from (meta)genomes. Interestingly, 60 - 95% of all phage sequences share no homology to current annotated proteins. As a result, a large proportion of phage genes are annotated as hypothetical. This reality heavily affects the annotation of both structural and auxiliary metabolic genes. Here we present phenomic methods designed to capture the physiological response(s) of a selected host during expression of one of these unknown phage genes. Multi-phenotype Assay Plates (MAPs) are used to monitor the diversity of host substrate utilization and subsequent biomass formation, while metabolomics provides bi-product analysismore » by monitoring metabolite abundance and diversity. Both tools are used simultaneously to provide a phenotypic profile associated with expression of a single putative phage open reading frame (ORF). Thus, representative results for both methods are compared, highlighting the phenotypic profile differences of a host carrying either putative structural or metabolic phage genes. In addition, the visualization techniques and high throughput computational pipelines that facilitated experimental analysis are presented.« less

Phenotype analysis of congenital and neurodevelopmental disorders in the next generation sequencing era.

PubMed

Carey, John C

2017-09-01

The designation, phenotype, was proposed as a term by Wilhelm Johannsen in 1909. The word is derived from the Greek, phano (showing) and typo (type), phanotypos. Phenotype has become a widely recognized term, even outside of the genetics community, in recent years with the ongoing identification of human disease genes. The term has been defined as the observable constitution of an organism, but sometimes refers to a condition when a person has a particular clinical presentation. Analysis of phenotype is a timely theme because advances in the understanding of the genetic basis of human disease and the emergence of next generation sequencing have spurred a renewed interest in phenotype and the proposal to establish a "Human Phenome Project." This article summarizes the principles of phenotype analysis that are important in medical genetics and describes approaches to comprehensive phenotype analysis in the investigation of patients with human disorders. I discuss the various elements related to disease phenotypes and highlight neurofibromatosis type 1 and the Elements of Morphology Project as illustrations of the principles. In recent years, the notion of "deep phenotyping" has emerged. Currently there are now a number of proposed strategies and resources to approach this concept. Not since the 1960s and 1970s has there been such an exciting time in the history of medicine surrounding the analysis of phenotype in genetic disorders. © 2017 Wiley Periodicals, Inc.

Cancer Imaging Phenomics Software Suite: Application to Brain and Breast Cancer | Informatics Technology for Cancer Research (ITCR)

Cancer.gov

The transition of oncologic imaging from its “industrial era” to it is “information era” demands analytical methods that 1) extract information from this data that is clinically and biologically relevant; 2) integrate imaging, clinical, and genomic data via rigorous statistical and computational methodologies in order to derive models valuable for understanding cancer mechanisms, diagnosis, prognostic assessment, response evaluation, and personalized treatment management; 3) are available to the biomedical community for easy use and application, with the aim of understanding, diagnosing, an

An Integrated Molecular Database on Indian Insects.

PubMed

Pratheepa, Maria; Venkatesan, Thiruvengadam; Gracy, Gandhi; Jalali, Sushil Kumar; Rangheswaran, Rajagopal; Antony, Jomin Cruz; Rai, Anil

2018-01-01

MOlecular Database on Indian Insects (MODII) is an online database linking several databases like Insect Pest Info, Insect Barcode Information System (IBIn), Insect Whole Genome sequence, Other Genomic Resources of National Bureau of Agricultural Insect Resources (NBAIR), Whole Genome sequencing of Honey bee viruses, Insecticide resistance gene database and Genomic tools. This database was developed with a holistic approach for collecting information about phenomic and genomic information of agriculturally important insects. This insect resource database is available online for free at http://cib.res.in. http://cib.res.in/.

An Integrated Systems Genetics and Omics Toolkit to Probe Gene Function.

PubMed

Li, Hao; Wang, Xu; Rukina, Daria; Huang, Qingyao; Lin, Tao; Sorrentino, Vincenzo; Zhang, Hongbo; Bou Sleiman, Maroun; Arends, Danny; McDaid, Aaron; Luan, Peiling; Ziari, Naveed; Velázquez-Villegas, Laura A; Gariani, Karim; Kutalik, Zoltan; Schoonjans, Kristina; Radcliffe, Richard A; Prins, Pjotr; Morgenthaler, Stephan; Williams, Robert W; Auwerx, Johan

2018-01-24

Identifying genetic and environmental factors that impact complex traits and common diseases is a high biomedical priority. Here, we developed, validated, and implemented a series of multi-layered systems approaches, including (expression-based) phenome-wide association, transcriptome-/proteome-wide association, and (reverse-) mediation analysis, in an open-access web server (systems-genetics.org) to expedite the systems dissection of gene function. We applied these approaches to multi-omics datasets from the BXD mouse genetic reference population, and identified and validated associations between genes and clinical and molecular phenotypes, including previously unreported links between Rpl26 and body weight, and Cpt1a and lipid metabolism. Furthermore, through mediation and reverse-mediation analysis we established regulatory relations between genes, such as the co-regulation of BCKDHA and BCKDHB protein levels, and identified targets of transcription factors E2F6, ZFP277, and ZKSCAN1. Our multifaceted toolkit enabled the identification of gene-gene and gene-phenotype links that are robust and that translate well across populations and species, and can be universally applied to any populations with multi-omics datasets. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Polymicrogyria-associated epilepsy: a multi-center phenotypic study from the Epilepsy Phenome/Genome Project

PubMed Central

Shain, Catherine; Ramgopal, Sriram; Fallil, Zianka; Parulkar, Isha; Alongi, Richard; Knowlton, Robert; Poduri, Annapurna

2013-01-01

Purpose Polymicrogyria (PMG) is an epileptogenic malformation of cortical development. We describe the clinical epilepsy and imaging features of a large cohort with PMG-related epilepsy. Methods Participants were recruited through the Epilepsy Phenome/Genome Project, a multi-center collaborative effort to collect detailed phenotypic data on individuals with epilepsy. We reviewed phenotypic data from participants with epilepsy and PMG. Key Findings We identified 87 participants, 43 female and 44 male, with PMG and epilepsy. Median age of seizure onset was 3 years (range <1 month-37 years). Most presented with focal epilepsy (87.4%), some in combination with seizures generalized from onset (23.0%). Focal seizures with dyscognitive features were most common (54.3%). Of those presenting with generalized seizure types, infantile spasms were most prevalent (45.2%). The most common topographic pattern was perisylvian PMG (77.0%), of which the majority was bilateral (56.7%). Generalized PMG presented with an earlier age of seizure onset (median age of 8 months) and an increased prevalence of developmental delay prior to seizure onset (57.1%). Of the focal, unilateral and asymmetric bilateral groups where PMG was more involved in one hemisphere, the majority (71.4%) of participants had seizures that lateralized to the same hemisphere as the PMG or the hemisphere with greater involvement. Significance Participants with PMG had both focal and generalized onset of seizures. Our data confirm the involvement of known topographic patterns of PMG and suggest that more extensive distributions of PMG present with an earlier age of seizure onset and increased prevalence of developmental delay prior to seizure onset. PMID:23750890

The challenges, advantages and future of phenome-wide association studies.

PubMed

Hebbring, Scott J

2014-02-01

Over the last decade, significant technological breakthroughs have revolutionized human genomic research in the form of genome-wide association studies (GWASs). GWASs have identified thousands of statistically significant genetic variants associated with hundreds of human conditions including many with immunological aetiologies (e.g. multiple sclerosis, ankylosing spondylitis and rheumatoid arthritis). Unfortunately, most GWASs fail to identify clinically significant associations. Identifying biologically significant variants by GWAS also presents a challenge. The GWAS is a phenotype-to-genotype approach. As a complementary/alternative approach to the GWAS, investigators have begun to exploit extensive electronic medical record systems to conduct a genotype-to-phenotype approach when studying human disease - specifically, the phenome-wide association study (PheWAS). Although the PheWAS approach is in its infancy, this method has already demonstrated its capacity to rediscover important genetic associations related to immunological diseases/conditions. Furthermore, PheWAS has the advantage of identifying genetic variants with pleiotropic properties. This is particularly relevant for HLA variants. For example, PheWAS results have demonstrated that the HLA-DRB1 variant associated with multiple sclerosis may also be associated with erythematous conditions including rosacea. Likewise, PheWAS has demonstrated that the HLA-B genotype is not only associated with spondylopathies, uveitis, and variability in platelet count, but may also play an important role in other conditions, such as mastoiditis. This review will discuss and compare general PheWAS methodologies, describe both the challenges and advantages of the PheWAS, and provide insight into the potential directions in which PheWAS may lead. © 2013 The Authors. Immunology Published by John Wiley & Sons Ltd.

A high-throughput screening system for barley/powdery mildew interactions based on automated analysis of light micrographs.

PubMed

Ihlow, Alexander; Schweizer, Patrick; Seiffert, Udo

2008-01-23

To find candidate genes that potentially influence the susceptibility or resistance of crop plants to powdery mildew fungi, an assay system based on transient-induced gene silencing (TIGS) as well as transient over-expression in single epidermal cells of barley has been developed. However, this system relies on quantitative microscopic analysis of the barley/powdery mildew interaction and will only become a high-throughput tool of phenomics upon automation of the most time-consuming steps. We have developed a high-throughput screening system based on a motorized microscope which evaluates the specimens fully automatically. A large-scale double-blind verification of the system showed an excellent agreement of manual and automated analysis and proved the system to work dependably. Furthermore, in a series of bombardment experiments an RNAi construct targeting the Mlo gene was included, which is expected to phenocopy resistance mediated by recessive loss-of-function alleles such as mlo5. In most cases, the automated analysis system recorded a shift towards resistance upon RNAi of Mlo, thus providing proof of concept for its usefulness in detecting gene-target effects. Besides saving labor and enabling a screening of thousands of candidate genes, this system offers continuous operation of expensive laboratory equipment and provides a less subjective analysis as well as a complete and enduring documentation of the experimental raw data in terms of digital images. In general, it proves the concept of enabling available microscope hardware to handle challenging screening tasks fully automatically.

Plant functional genomics

NASA Astrophysics Data System (ADS)

Holtorf, Hauke; Guitton, Marie-Christine; Reski, Ralf

2002-04-01

Functional genome analysis of plants has entered the high-throughput stage. The complete genome information from key species such as Arabidopsis thaliana and rice is now available and will further boost the application of a range of new technologies to functional plant gene analysis. To broadly assign functions to unknown genes, different fast and multiparallel approaches are currently used and developed. These new technologies are based on known methods but are adapted and improved to accommodate for comprehensive, large-scale gene analysis, i.e. such techniques are novel in the sense that their design allows researchers to analyse many genes at the same time and at an unprecedented pace. Such methods allow analysis of the different constituents of the cell that help to deduce gene function, namely the transcripts, proteins and metabolites. Similarly the phenotypic variations of entire mutant collections can now be analysed in a much faster and more efficient way than before. The different methodologies have developed to form their own fields within the functional genomics technological platform and are termed transcriptomics, proteomics, metabolomics and phenomics. Gene function, however, cannot solely be inferred by using only one such approach. Rather, it is only by bringing together all the information collected by different functional genomic tools that one will be able to unequivocally assign functions to unknown plant genes. This review focuses on current technical developments and their impact on the field of plant functional genomics. The lower plant Physcomitrella is introduced as a new model system for gene function analysis, owing to its high rate of homologous recombination.

Phenome-Wide Association Study of Rheumatoid Arthritis Subgroups Identifies Association between Seronegative Disease and Fibromyalgia

PubMed Central

Doss, Jayanth; Mo, Huan; Carroll, Robert J.; Crofford, Leslie J.; Denny, Joshua C.

2016-01-01

Objective The differences between seronegative and seropositive rheumatoid arthritis (RA) have not been widely reported. We performed electronic health record (EHR)-based phenome-wide association studies (PheWAS) to identify disease associations in seropositive and seronegative RA. Methods A validated algorithm identified RA subjects from the de-identified EHR. Serotypes were determined by values of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA). We tested EHR-derived phenotypes using PheWAS comparing seropositive RA against seronegative RA, yielding disease associations. PheWAS was also performed on RF-positive versus RF-negative subjects and ACPA-positive versus ACPA-negative subjects. Following PheWAS, select phenotypes were then manually reviewed and fibromyalgia was specifically evaluated using a validated algorithm. Results There were 2199 individuals identified with RA and either RF or ACPA testing. Of these, 1382 (63%) were seropositive. Seronegative RA was associated with “Myalgia and Myositis” (odds ratio [OR] 2.1, P=3.7×10−10) and back pain. A manual record review showed 80% of Myalgia and Myositis codes were used for fibromyalgia, and follow-up with a specific EHR algorithm for fibromyalgia confirmed that seronegative RA was associated with fibromyalgia (OR=1.8, P=4.0×10−6). Seropositive RA was associated with Chronic Airway Obstruction (OR=2.2, P=1.4×10−4) and tobacco use (OR=2.2, P=7.0×10−4). Conclusion This PheWAS in RA patients identifies a strong association between seronegativity and fibromyalgia. It also affirms relationships between seropositivity with chronic airway obstruction and seropositivity with tobacco use. These findings demonstrate the utility of the PheWAS approach to discover novel phenotype associations within different subgroups of a disease. PMID:27589350

Multi-level evaluation of Escherichia coli polyphosphate related mutants using global transcriptomic, proteomic and phenomic analyses.

PubMed

Varas, Macarena; Valdivieso, Camilo; Mauriaca, Cecilia; Ortíz-Severín, Javiera; Paradela, Alberto; Poblete-Castro, Ignacio; Cabrera, Ricardo; Chávez, Francisco P

2017-04-01

Polyphosphate (polyP) is a linear biopolymer found in all living cells. In bacteria, mutants lacking polyphosphate kinase 1 (PPK1), the enzyme responsible for synthesis of most polyP, have many structural and functional defects. However, little is known about the causes of these pleiotropic alterations. The link between ppk1 deletion and those numerous phenotypes observed can be the result of complex molecular interactions that can be elucidated via a systems biology approach. By integrating different omics levels (transcriptome, proteome and phenome), we described the functioning of various metabolic pathways among Escherichia coli polyphosphate mutant strains (Δppk1, Δppx, and ΔpolyP). Bioinformatic analyses reveal the complex metabolic and regulatory bases of the phenotypes unique to polyP mutants. Our results suggest that during polyP deficiency (Δppk1 mutant), metabolic pathways needed for energy supply are up-regulated, including fermentation, aerobic and anaerobic respiration. Transcriptomic and q-proteomic contrasting changes between Δppk1 and Δppx mutant strains were observed in those central metabolic pathways and confirmed by using Phenotypic microarrays. In addition, our results suggest a regulatory connection between polyP, second messenger metabolism, alternative Sigma/Anti-Sigma factors and type-II toxin-antitoxin (TA) systems. We suggest a broader role for polyP via regulation of ATP-dependent proteolysis of type II toxin-antitoxin system and alternative Sigma/Anti-Sigma factors, that could explain the multiple structural and functional deficiencies described due to alteration of polyP metabolism. Understanding the interplay of polyP in bacterial metabolism using a systems biology approach can help to improve design of novel antimicrobials toward pathogens. Copyright © 2017 Elsevier B.V. All rights reserved.

Image Harvest: an open-source platform for high-throughput plant image processing and analysis

PubMed Central

Knecht, Avi C.; Campbell, Malachy T.; Caprez, Adam; Swanson, David R.; Walia, Harkamal

2016-01-01

High-throughput plant phenotyping is an effective approach to bridge the genotype-to-phenotype gap in crops. Phenomics experiments typically result in large-scale image datasets, which are not amenable for processing on desktop computers, thus creating a bottleneck in the image-analysis pipeline. Here, we present an open-source, flexible image-analysis framework, called Image Harvest (IH), for processing images originating from high-throughput plant phenotyping platforms. Image Harvest is developed to perform parallel processing on computing grids and provides an integrated feature for metadata extraction from large-scale file organization. Moreover, the integration of IH with the Open Science Grid provides academic researchers with the computational resources required for processing large image datasets at no cost. Image Harvest also offers functionalities to extract digital traits from images to interpret plant architecture-related characteristics. To demonstrate the applications of these digital traits, a rice (Oryza sativa) diversity panel was phenotyped and genome-wide association mapping was performed using digital traits that are used to describe different plant ideotypes. Three major quantitative trait loci were identified on rice chromosomes 4 and 6, which co-localize with quantitative trait loci known to regulate agronomically important traits in rice. Image Harvest is an open-source software for high-throughput image processing that requires a minimal learning curve for plant biologists to analyzephenomics datasets. PMID:27141917

Constitutional Mosaic Trisomy 13 in Two Germ Cell Layers is Different from Patau Syndrome? A Case Report.

PubMed

Kunwar, Fulesh; Pandya, Vidhi; Bakshi, Sonal R

2016-03-01

The heterogeneous phenotype of known syndromes is a clinical challenge, and harmonized description using globally accepted ontology is desirable. This report attempts phenotypic analysis in a patient of constitutional mosaic trisomy 13 in mesoderm and ectoderm to make globally comparable clinical description. Phenotypic features (minor/major abnormalities) were recorded and matched with the Human Phenotype Ontology terms that were used to query web-based tool Phenomizer. We report here a case of 24-year-old girl born to non consanguineous parents with history of one abortion. Her phenotypic evaluation included short columella, low-set ears, seizures, enlarged naris, bifid tongue, infra-orbital fold, smooth philtrum, microtia, microcephaly, carious teeth, downslanted palpebral fissures, proportionate short stature, high palate, thin upper lip vermilion, small for gestational age, broad fingertip, broad hallux, mandibular prognathia and dental malocclusion. Karyotype and interphase FISH (Fluorescence in situ hybridization) was done in blood cells. Interphase FISH was also performed on buccal epithelial cells. Cytogenetic analysis demonstrated trisomy 13 mosaicism in 25% cells i.e. 47, XX,+13(9)/46,XX(27). The interphase FISH in blood cells showed trisomy 13 in 15%, whereas in buccal mucosa cells showed nearly 6%. Mosaic aneuploidy in constitutional karyotype can be responsible for variation in clinical and morphological presentation of patient with genetic disorder.

GWAS in a Box: Statistical and Visual Analytics of Structured Associations via GenAMap

PubMed Central

Xing, Eric P.; Curtis, Ross E.; Schoenherr, Georg; Lee, Seunghak; Yin, Junming; Puniyani, Kriti; Wu, Wei; Kinnaird, Peter

2014-01-01

With the continuous improvement in genotyping and molecular phenotyping technology and the decreasing typing cost, it is expected that in a few years, more and more clinical studies of complex diseases will recruit thousands of individuals for pan-omic genetic association analyses. Hence, there is a great need for algorithms and software tools that could scale up to the whole omic level, integrate different omic data, leverage rich structure information, and be easily accessible to non-technical users. We present GenAMap, an interactive analytics software platform that 1) automates the execution of principled machine learning methods that detect genome- and phenome-wide associations among genotypes, gene expression data, and clinical or other macroscopic traits, and 2) provides new visualization tools specifically designed to aid in the exploration of association mapping results. Algorithmically, GenAMap is based on a new paradigm for GWAS and PheWAS analysis, termed structured association mapping, which leverages various structures in the omic data. We demonstrate the function of GenAMap via a case study of the Brem and Kruglyak yeast dataset, and then apply it on a comprehensive eQTL analysis of the NIH heterogeneous stock mice dataset and report some interesting findings. GenAMap is available from http://sailing.cs.cmu.edu/genamap. PMID:24905018

Towards building a disease-phenotype knowledge base: extracting disease-manifestation relationship from literature

PubMed Central

Xu, Rong; Li, Li; Wang, QuanQiu

2013-01-01

Motivation: Systems approaches to studying phenotypic relationships among diseases are emerging as an active area of research for both novel disease gene discovery and drug repurposing. Currently, systematic study of disease phenotypic relationships on a phenome-wide scale is limited because large-scale machine-understandable disease–phenotype relationship knowledge bases are often unavailable. Here, we present an automatic approach to extract disease–manifestation (D-M) pairs (one specific type of disease–phenotype relationship) from the wide body of published biomedical literature. Data and Methods: Our method leverages external knowledge and limits the amount of human effort required. For the text corpus, we used 119 085 682 MEDLINE sentences (21 354 075 citations). First, we used D-M pairs from existing biomedical ontologies as prior knowledge to automatically discover D-M–specific syntactic patterns. We then extracted additional pairs from MEDLINE using the learned patterns. Finally, we analysed correlations between disease manifestations and disease-associated genes and drugs to demonstrate the potential of this newly created knowledge base in disease gene discovery and drug repurposing. Results: In total, we extracted 121 359 unique D-M pairs with a high precision of 0.924. Among the extracted pairs, 120 419 (99.2%) have not been captured in existing structured knowledge sources. We have shown that disease manifestations correlate positively with both disease-associated genes and drug treatments. Conclusions: The main contribution of our study is the creation of a large-scale and accurate D-M phenotype relationship knowledge base. This unique knowledge base, when combined with existing phenotypic, genetic and proteomic datasets, can have profound implications in our deeper understanding of disease etiology and in rapid drug repurposing. Availability: http://nlp.case.edu/public/data/DMPatternUMLS/ Contact: rxx@case.edu PMID:23828786

Leaf phenomics: a systematic reverse genetic screen for Arabidopsis leaf mutants.

PubMed

Wilson-Sánchez, David; Rubio-Díaz, Silvia; Muñoz-Viana, Rafael; Pérez-Pérez, José Manuel; Jover-Gil, Sara; Ponce, María Rosa; Micol, José Luis

2014-09-01

The study and eventual manipulation of leaf development in plants requires a thorough understanding of the genetic basis of leaf organogenesis. Forward genetic screens have identified hundreds of Arabidopsis mutants with altered leaf development, but the genome has not yet been saturated. To identify genes required for leaf development we are screening the Arabidopsis Salk Unimutant collection. We have identified 608 lines that exhibit a leaf phenotype with full penetrance and almost constant expressivity and 98 additional lines with segregating mutant phenotypes. To allow indexing and integration with other mutants, the mutant phenotypes were described using a custom leaf phenotype ontology. We found that the indexed mutation is present in the annotated locus for 78% of the 553 mutants genotyped, and that in half of these the annotated T-DNA is responsible for the phenotype. To quickly map non-annotated T-DNA insertions, we developed a reliable, cost-effective and easy method based on whole-genome sequencing. To enable comprehensive access to our data, we implemented a public web application named PhenoLeaf (http://genetics.umh.es/phenoleaf) that allows researchers to query the results of our screen, including text and visual phenotype information. We demonstrated how this new resource can facilitate gene function discovery by identifying and characterizing At1g77600, which we found to be required for proximal-distal cell cycle-driven leaf growth, and At3g62870, which encodes a ribosomal protein needed for cell proliferation and chloroplast function. This collection provides a valuable tool for the study of leaf development, characterization of biomass feedstocks and examination of other traits in this fundamental photosynthetic organ. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

Enhancing Insights into Pulmonary Vascular Disease through a Precision Medicine Approach. A Joint NHLBI-Cardiovascular Medical Research and Education Fund Workshop Report.

PubMed

Newman, John H; Rich, Stuart; Abman, Steven H; Alexander, John H; Barnard, John; Beck, Gerald J; Benza, Raymond L; Bull, Todd M; Chan, Stephen Y; Chun, Hyung J; Doogan, Declan; Dupuis, Jocelyn; Erzurum, Serpil C; Frantz, Robert P; Geraci, Mark; Gillies, Hunter; Gladwin, Mark; Gray, Michael P; Hemnes, Anna R; Herbst, Roy S; Hernandez, Adrian F; Hill, Nicholas S; Horn, Evelyn M; Hunter, Kendall; Jing, Zhi-Cheng; Johns, Roger; Kaul, Sanjay; Kawut, Steven M; Lahm, Tim; Leopold, Jane A; Lewis, Greg D; Mathai, Stephen C; McLaughlin, Vallerie V; Michelakis, Evangelos D; Nathan, Steven D; Nichols, William; Page, Grier; Rabinovitch, Marlene; Rich, Jonathan; Rischard, Franz; Rounds, Sharon; Shah, Sanjiv J; Tapson, Victor F; Lowy, Naomi; Stockbridge, Norman; Weinmann, Gail; Xiao, Lei

2017-06-15

The Division of Lung Diseases of the NHLBI and the Cardiovascular Medical Education and Research Fund held a workshop to discuss how to leverage the anticipated scientific output from the recently launched "Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics" (PVDOMICS) program to develop newer approaches to pulmonary vascular disease. PVDOMICS is a collaborative, protocol-driven network to analyze all patient populations with pulmonary hypertension to define novel pulmonary vascular disease (PVD) phenotypes. Stakeholders, including basic, translational, and clinical investigators; clinicians; patient advocacy organizations; regulatory agencies; and pharmaceutical industry experts, joined to discuss the application of precision medicine to PVD clinical trials. Recommendations were generated for discussion of research priorities in line with NHLBI Strategic Vision Goals that include: (1) A national effort, involving all the stakeholders, should seek to coordinate biosamples and biodata from all funded programs to a web-based repository so that information can be shared and correlated with other research projects. Example programs sponsored by NHLBI include PVDOMICS, Pulmonary Hypertension Breakthrough Initiative, the National Biological Sample and Data Repository for PAH, and the National Precision Medicine Initiative. (2) A task force to develop a master clinical trials protocol for PVD to apply precision medicine principles to future clinical trials. Specific features include: (a) adoption of smaller clinical trials that incorporate biomarker-guided enrichment strategies, using adaptive and innovative statistical designs; and (b) development of newer endpoints that reflect well-defined and clinically meaningful changes. (3) Development of updated and systematic variables in imaging, hemodynamic, cellular, genomic, and metabolic tests that will help precisely identify individual and shared features of PVD and serve as the basis of novel phenotypes for therapeutic interventions.

Resources and Recommendations for Using Transcriptomics to Address Grand Challenges in Comparative Biology

PubMed Central

Mykles, Donald L.; Burnett, Karen G.; Durica, David S.; Joyce, Blake L.; McCarthy, Fiona M.; Schmidt, Carl J.; Stillman, Jonathon H.

2016-01-01

High-throughput RNA sequencing (RNA-seq) technology has become an important tool for studying physiological responses of organisms to changes in their environment. De novo assembly of RNA-seq data has allowed researchers to create a comprehensive catalog of genes expressed in a tissue and to quantify their expression without a complete genome sequence. The contributions from the “Tapping the Power of Crustacean Transcriptomics to Address Grand Challenges in Comparative Biology” symposium in this issue show the successes and limitations of using RNA-seq in the study of crustaceans. In conjunction with the symposium, the Animal Genome to Phenome Research Coordination Network collated comments from participants at the meeting regarding the challenges encountered when using transcriptomics in their research. Input came from novices and experts ranging from graduate students to principal investigators. Many were unaware of the bioinformatics analysis resources currently available on the CyVerse platform. Our analysis of community responses led to three recommendations for advancing the field: (1) integration of genomic and RNA-seq sequence assemblies for crustacean gene annotation and comparative expression; (2) development of methodologies for the functional analysis of genes; and (3) information and training exchange among laboratories for transmission of best practices. The field lacks the methods for manipulating tissue-specific gene expression. The decapod crustacean research community should consider the cherry shrimp, Neocaridina denticulata, as a decapod model for the application of transgenic tools for functional genomics. This would require a multi-investigator effort. PMID:27639274

Image Harvest: an open-source platform for high-throughput plant image processing and analysis.

PubMed

Knecht, Avi C; Campbell, Malachy T; Caprez, Adam; Swanson, David R; Walia, Harkamal

2016-05-01

High-throughput plant phenotyping is an effective approach to bridge the genotype-to-phenotype gap in crops. Phenomics experiments typically result in large-scale image datasets, which are not amenable for processing on desktop computers, thus creating a bottleneck in the image-analysis pipeline. Here, we present an open-source, flexible image-analysis framework, called Image Harvest (IH), for processing images originating from high-throughput plant phenotyping platforms. Image Harvest is developed to perform parallel processing on computing grids and provides an integrated feature for metadata extraction from large-scale file organization. Moreover, the integration of IH with the Open Science Grid provides academic researchers with the computational resources required for processing large image datasets at no cost. Image Harvest also offers functionalities to extract digital traits from images to interpret plant architecture-related characteristics. To demonstrate the applications of these digital traits, a rice (Oryza sativa) diversity panel was phenotyped and genome-wide association mapping was performed using digital traits that are used to describe different plant ideotypes. Three major quantitative trait loci were identified on rice chromosomes 4 and 6, which co-localize with quantitative trait loci known to regulate agronomically important traits in rice. Image Harvest is an open-source software for high-throughput image processing that requires a minimal learning curve for plant biologists to analyzephenomics datasets. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Meta-analysis of correlated traits via summary statistics from GWASs with an application in hypertension.

PubMed

Zhu, Xiaofeng; Feng, Tao; Tayo, Bamidele O; Liang, Jingjing; Young, J Hunter; Franceschini, Nora; Smith, Jennifer A; Yanek, Lisa R; Sun, Yan V; Edwards, Todd L; Chen, Wei; Nalls, Mike; Fox, Ervin; Sale, Michele; Bottinger, Erwin; Rotimi, Charles; Liu, Yongmei; McKnight, Barbara; Liu, Kiang; Arnett, Donna K; Chakravati, Aravinda; Cooper, Richard S; Redline, Susan

2015-01-08

Genome-wide association studies (GWASs) have identified many genetic variants underlying complex traits. Many detected genetic loci harbor variants that associate with multiple-even distinct-traits. Most current analysis approaches focus on single traits, even though the final results from multiple traits are evaluated together. Such approaches miss the opportunity to systemically integrate the phenome-wide data available for genetic association analysis. In this study, we propose a general approach that can integrate association evidence from summary statistics of multiple traits, either correlated, independent, continuous, or binary traits, which might come from the same or different studies. We allow for trait heterogeneity effects. Population structure and cryptic relatedness can also be controlled. Our simulations suggest that the proposed method has improved statistical power over single-trait analysis in most of the cases we studied. We applied our method to the Continental Origins and Genetic Epidemiology Network (COGENT) African ancestry samples for three blood pressure traits and identified four loci (CHIC2, HOXA-EVX1, IGFBP1/IGFBP3, and CDH17; p < 5.0 × 10(-8)) associated with hypertension-related traits that were missed by a single-trait analysis in the original report. Six additional loci with suggestive association evidence (p < 5.0 × 10(-7)) were also observed, including CACNA1D and WNT3. Our study strongly suggests that analyzing multiple phenotypes can improve statistical power and that such analysis can be executed with the summary statistics from GWASs. Our method also provides a way to study a cross phenotype (CP) association by using summary statistics from GWASs of multiple phenotypes. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

CHALLENGES IN PHENOTYPE DEFINITION IN THE WHOLE-GENOME ERA: MULTIVARIATE MODELS OF MEMORY AND INTELLIGENCE

PubMed Central

SABB, F. W.; BURGGREN, A. C.; HIGIER, R. G.; FOX, J.; HE, J.; PARKER, D. S.; POLDRACK, R. A.; CHU, W.; CANNON, T. D.; FREIMER, N. B.; BILDER, R. M.

2009-01-01

Refining phenotypes for the study of neuropsychiatric disorders is of paramount importance in neuroscience. Poor phenotype definition provides the greatest obstacle for making progress in disorders like schizophrenia, bipolar disorder, Attention Deficit/Hyperactivity Disorder (ADHD), and autism. Using freely available informatics tools developed by the Consortium for Neuropsychiatric Phenomics (CNP), we provide a framework for defining and refining latent constructs used in neuroscience research and then apply this strategy to review known genetic contributions to memory and intelligence in healthy individuals. This approach can help us begin to build multi-level phenotype models that express the interactions between constructs necessary to understand complex neuropsychiatric diseases. PMID:19450667

Stress-tolerance of baker's-yeast (Saccharomyces cerevisiae) cells: stress-protective molecules and genes involved in stress tolerance.

PubMed

Shima, Jun; Takagi, Hiroshi

2009-05-29

During the fermentation of dough and the production of baker's yeast (Saccharomyces cerevisiae), cells are exposed to numerous environmental stresses (baking-associated stresses) such as freeze-thaw, high sugar concentrations, air-drying and oxidative stresses. Cellular macromolecules, including proteins, nucleic acids and membranes, are seriously damaged under stress conditions, leading to the inhibition of cell growth, cell viability and fermentation. To avoid lethal damage, yeast cells need to acquire a variety of stress-tolerant mechanisms, for example the induction of stress proteins, the accumulation of stress protectants, changes in membrane composition and repression of translation, and by regulating the corresponding gene expression via stress-triggered signal-transduction pathways. Trehalose and proline are considered to be critical stress protectants, as is glycerol. It is known that these molecules are effective for providing protection against various types of environmental stresses. Modifications of the metabolic pathways of trehalose and proline by self-cloning methods have significantly increased tolerance to baking-associated stresses. To clarify which genes are required for stress tolerance, both a comprehensive phenomics analysis and a functional genomics analysis were carried out under stress conditions that simulated those occurring during the commercial baking process. These analyses indicated that many genes are involved in stress tolerance in yeast. In particular, it was suggested that vacuolar H+-ATPase plays important roles in yeast cells under stress conditions.

Constitutional Mosaic Trisomy 13 in Two Germ Cell Layers is Different from Patau Syndrome? A Case Report

PubMed Central

Kunwar, Fulesh; Pandya, Vidhi

2016-01-01

The heterogeneous phenotype of known syndromes is a clinical challenge, and harmonized description using globally accepted ontology is desirable. This report attempts phenotypic analysis in a patient of constitutional mosaic trisomy 13 in mesoderm and ectoderm to make globally comparable clinical description. Phenotypic features (minor/major abnormalities) were recorded and matched with the Human Phenotype Ontology terms that were used to query web-based tool Phenomizer. We report here a case of 24-year-old girl born to non consanguineous parents with history of one abortion. Her phenotypic evaluation included short columella, low-set ears, seizures, enlarged naris, bifid tongue, infra-orbital fold, smooth philtrum, microtia, microcephaly, carious teeth, downslanted palpebral fissures, proportionate short stature, high palate, thin upper lip vermilion, small for gestational age, broad fingertip, broad hallux, mandibular prognathia and dental malocclusion. Karyotype and interphase FISH (Fluorescence in situ hybridization) was done in blood cells. Interphase FISH was also performed on buccal epithelial cells. Cytogenetic analysis demonstrated trisomy 13 mosaicism in 25% cells i.e. 47, XX,+13(9)/46,XX(27). The interphase FISH in blood cells showed trisomy 13 in 15%, whereas in buccal mucosa cells showed nearly 6%. Mosaic aneuploidy in constitutional karyotype can be responsible for variation in clinical and morphological presentation of patient with genetic disorder. PMID:27134897

Data Sources for Trait Databases: Comparing the Phenomic Content of Monographs and Evolutionary Matrices.

PubMed

Dececchi, T Alex; Mabee, Paula M; Blackburn, David C

2016-01-01

Databases of organismal traits that aggregate information from one or multiple sources can be leveraged for large-scale analyses in biology. Yet the differences among these data streams and how well they capture trait diversity have never been explored. We present the first analysis of the differences between phenotypes captured in free text of descriptive publications ('monographs') and those used in phylogenetic analyses ('matrices'). We focus our analysis on osteological phenotypes of the limbs of four extinct vertebrate taxa critical to our understanding of the fin-to-limb transition. We find that there is low overlap between the anatomical entities used in these two sources of phenotype data, indicating that phenotypes represented in matrices are not simply a subset of those found in monographic descriptions. Perhaps as expected, compared to characters found in matrices, phenotypes in monographs tend to emphasize descriptive and positional morphology, be somewhat more complex, and relate to fewer additional taxa. While based on a small set of focal taxa, these qualitative and quantitative data suggest that either source of phenotypes alone will result in incomplete knowledge of variation for a given taxon. As a broader community develops to use and expand databases characterizing organismal trait diversity, it is important to recognize the limitations of the data sources and develop strategies to more fully characterize variation both within species and across the tree of life.

Data Sources for Trait Databases: Comparing the Phenomic Content of Monographs and Evolutionary Matrices

PubMed Central

Dececchi, T. Alex; Mabee, Paula M.; Blackburn, David C.

2016-01-01

Databases of organismal traits that aggregate information from one or multiple sources can be leveraged for large-scale analyses in biology. Yet the differences among these data streams and how well they capture trait diversity have never been explored. We present the first analysis of the differences between phenotypes captured in free text of descriptive publications (‘monographs’) and those used in phylogenetic analyses (‘matrices’). We focus our analysis on osteological phenotypes of the limbs of four extinct vertebrate taxa critical to our understanding of the fin-to-limb transition. We find that there is low overlap between the anatomical entities used in these two sources of phenotype data, indicating that phenotypes represented in matrices are not simply a subset of those found in monographic descriptions. Perhaps as expected, compared to characters found in matrices, phenotypes in monographs tend to emphasize descriptive and positional morphology, be somewhat more complex, and relate to fewer additional taxa. While based on a small set of focal taxa, these qualitative and quantitative data suggest that either source of phenotypes alone will result in incomplete knowledge of variation for a given taxon. As a broader community develops to use and expand databases characterizing organismal trait diversity, it is important to recognize the limitations of the data sources and develop strategies to more fully characterize variation both within species and across the tree of life. PMID:27191170

The evolution of self-control

PubMed Central

MacLean, Evan L.; Hare, Brian; Nunn, Charles L.; Addessi, Elsa; Amici, Federica; Anderson, Rindy C.; Aureli, Filippo; Baker, Joseph M.; Bania, Amanda E.; Barnard, Allison M.; Boogert, Neeltje J.; Brannon, Elizabeth M.; Bray, Emily E.; Bray, Joel; Brent, Lauren J. N.; Burkart, Judith M.; Call, Josep; Cantlon, Jessica F.; Cheke, Lucy G.; Clayton, Nicola S.; Delgado, Mikel M.; DiVincenti, Louis J.; Fujita, Kazuo; Herrmann, Esther; Hiramatsu, Chihiro; Jacobs, Lucia F.; Jordan, Kerry E.; Laude, Jennifer R.; Leimgruber, Kristin L.; Messer, Emily J. E.; de A. Moura, Antonio C.; Ostojić, Ljerka; Picard, Alejandra; Platt, Michael L.; Plotnik, Joshua M.; Range, Friederike; Reader, Simon M.; Reddy, Rachna B.; Sandel, Aaron A.; Santos, Laurie R.; Schumann, Katrin; Seed, Amanda M.; Sewall, Kendra B.; Shaw, Rachael C.; Slocombe, Katie E.; Su, Yanjie; Takimoto, Ayaka; Tan, Jingzhi; Tao, Ruoting; van Schaik, Carel P.; Virányi, Zsófia; Visalberghi, Elisabetta; Wade, Jordan C.; Watanabe, Arii; Widness, Jane; Young, Julie K.; Zentall, Thomas R.; Zhao, Yini

2014-01-01

Cognition presents evolutionary research with one of its greatest challenges. Cognitive evolution has been explained at the proximate level by shifts in absolute and relative brain volume and at the ultimate level by differences in social and dietary complexity. However, no study has integrated the experimental and phylogenetic approach at the scale required to rigorously test these explanations. Instead, previous research has largely relied on various measures of brain size as proxies for cognitive abilities. We experimentally evaluated these major evolutionary explanations by quantitatively comparing the cognitive performance of 567 individuals representing 36 species on two problem-solving tasks measuring self-control. Phylogenetic analysis revealed that absolute brain volume best predicted performance across species and accounted for considerably more variance than brain volume controlling for body mass. This result corroborates recent advances in evolutionary neurobiology and illustrates the cognitive consequences of cortical reorganization through increases in brain volume. Within primates, dietary breadth but not social group size was a strong predictor of species differences in self-control. Our results implicate robust evolutionary relationships between dietary breadth, absolute brain volume, and self-control. These findings provide a significant first step toward quantifying the primate cognitive phenome and explaining the process of cognitive evolution. PMID:24753565

Towards recommendations for metadata and data handling in plant phenotyping.

PubMed

Krajewski, Paweł; Chen, Dijun; Ćwiek, Hanna; van Dijk, Aalt D J; Fiorani, Fabio; Kersey, Paul; Klukas, Christian; Lange, Matthias; Markiewicz, Augustyn; Nap, Jan Peter; van Oeveren, Jan; Pommier, Cyril; Scholz, Uwe; van Schriek, Marco; Usadel, Björn; Weise, Stephan

2015-09-01

Recent methodological developments in plant phenotyping, as well as the growing importance of its applications in plant science and breeding, are resulting in a fast accumulation of multidimensional data. There is great potential for expediting both discovery and application if these data are made publicly available for analysis. However, collection and storage of phenotypic observations is not yet sufficiently governed by standards that would ensure interoperability among data providers and precisely link specific phenotypes and associated genomic sequence information. This lack of standards is mainly a result of a large variability of phenotyping protocols, the multitude of phenotypic traits that are measured, and the dependence of these traits on the environment. This paper discusses the current situation of standardization in the area of phenomics, points out the problems and shortages, and presents the areas that would benefit from improvement in this field. In addition, the foundations of the work that could revise the situation are proposed, and practical solutions developed by the authors are introduced. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Phenome-Wide Association Study of Rheumatoid Arthritis Subgroups Identifies Association Between Seronegative Disease and Fibromyalgia.

PubMed

Doss, Jayanth; Mo, Huan; Carroll, Robert J; Crofford, Leslie J; Denny, Joshua C

2017-02-01

The differences between seronegative and seropositive rheumatoid arthritis (RA) have not been widely reported. We performed electronic health record (EHR)-based phenome-wide association studies (PheWAS) to identify disease associations in seropositive and seronegative RA. A validated algorithm identified RA subjects from the de-identified version of the Vanderbilt University Medical Center EHR. Serotypes were determined by rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) values. We tested EHR-derived phenotypes using PheWAS comparing seropositive RA and seronegative RA, yielding disease associations. PheWAS was also performed in RF-positive versus RF-negative subjects and ACPA-positive versus ACPA-negative subjects. Following PheWAS, select phenotypes were then manually reviewed, and fibromyalgia was specifically evaluated using a validated algorithm. A total of 2,199 RA individuals with either RF or ACPA testing were identified. Of these, 1,382 patients (63%) were classified as seropositive. Seronegative RA was associated with myalgia and myositis (odds ratio [OR] 2.1, P = 3.7 × 10 -10 ) and back pain. A manual review of the health record showed that among subjects coded for Myalgia and Myositis, ∼80% had fibromyalgia. Follow-up with a specific EHR algorithm for fibromyalgia confirmed that seronegative RA was associated with fibromyalgia (OR 1.8, P = 4.0 × 10 -6 ). Seropositive RA was associated with chronic airway obstruction (OR 2.2, P = 1.4 × 10 -4 ) and tobacco use (OR 2.2, P = 7.0 × 10 -4 ). This PheWAS of RA patients identifies a strong association between seronegativity and fibromyalgia. It also affirms relationships between seropositivity and chronic airway obstruction and between seropositivity and tobacco use. These findings demonstrate the utility of the PheWAS approach to discover novel phenotype associations within different subgroups of a disease. © 2016, American College of Rheumatology.

Evidence of metabolic switching and implications for food safety from the phenome(s) of Salmonella enterica serovar Typhimurium DT104 cultured at selected points across the pork production food chain.

PubMed

Martins, Marta; McCusker, Matthew P; McCabe, Evonne M; O'Leary, Denis; Duffy, Geraldine; Fanning, Séamus

2013-09-01

Salmonella enterica serovar Typhimurium DT104 is a recognized food-borne pathogen that displays a multidrug-resistant phenotype and that is associated with systemic infections. At one extreme of the food chain, this bacterium can infect humans, limiting the treatment options available and thereby contributing to increased morbidity and mortality. Although the antibiotic resistance profile is well defined, little is known about other phenotypes that may be expressed by this pathogen at key points across the pork production food chain. In this study, 172 Salmonella enterica serovar Typhimurium DT104/DT104b isolated from an extensive "farm-to-fork" surveillance study, focusing on the pork food chain, were characterized in detail. Isolates were cultured from environmental, processing, retail, and clinical sources, and the study focused on phenotypes that may have contributed to persistence/survival in these different niches. Molecular subtypes, along with antibiotic resistance profiles, tolerance to biocides, motility, and biofilm formation, were determined. As a basis for human infection, acid survival and the ability to utilize a range of energy sources and to adhere to and/or invade Caco-2 cells were also studied. Comparative alterations to biocide tolerance were observed in isolates from retail. l-Tartaric acid and d-mannose-1-phosphate induced the formation of biofilms in a preselected subset of strains, independent of their origin. All clinical isolates were motile and demonstrated an enhanced ability to survive in acidic conditions. Our data report on a diverse phenotype, expressed by S. Typhimurium isolates cultured from the pork production food chain. Extending our understanding of the means by which this pathogen adapts to environmental niches along the "farm-to-fork" continuum will facilitate the protection of vulnerable consumers through targeted improvements in food safety measures.

Evidence of Metabolic Switching and Implications for Food Safety from the Phenome(s) of Salmonella enterica Serovar Typhimurium DT104 Cultured at Selected Points across the Pork Production Food Chain

PubMed Central

Martins, Marta; McCusker, Matthew P.; McCabe, Evonne M.; O'Leary, Denis; Duffy, Geraldine

2013-01-01

Salmonella enterica serovar Typhimurium DT104 is a recognized food-borne pathogen that displays a multidrug-resistant phenotype and that is associated with systemic infections. At one extreme of the food chain, this bacterium can infect humans, limiting the treatment options available and thereby contributing to increased morbidity and mortality. Although the antibiotic resistance profile is well defined, little is known about other phenotypes that may be expressed by this pathogen at key points across the pork production food chain. In this study, 172 Salmonella enterica serovar Typhimurium DT104/DT104b isolated from an extensive “farm-to-fork” surveillance study, focusing on the pork food chain, were characterized in detail. Isolates were cultured from environmental, processing, retail, and clinical sources, and the study focused on phenotypes that may have contributed to persistence/survival in these different niches. Molecular subtypes, along with antibiotic resistance profiles, tolerance to biocides, motility, and biofilm formation, were determined. As a basis for human infection, acid survival and the ability to utilize a range of energy sources and to adhere to and/or invade Caco-2 cells were also studied. Comparative alterations to biocide tolerance were observed in isolates from retail. l-Tartaric acid and d-mannose-1-phosphate induced the formation of biofilms in a preselected subset of strains, independent of their origin. All clinical isolates were motile and demonstrated an enhanced ability to survive in acidic conditions. Our data report on a diverse phenotype, expressed by S. Typhimurium isolates cultured from the pork production food chain. Extending our understanding of the means by which this pathogen adapts to environmental niches along the “farm-to-fork” continuum will facilitate the protection of vulnerable consumers through targeted improvements in food safety measures. PMID:23770904

Zebrafish models for translational neuroscience research: from tank to bedside

PubMed Central

Stewart, Adam Michael; Braubach, Oliver; Spitsbergen, Jan; Gerlai, Robert; Kalueff, Allan V.

2014-01-01

The zebrafish (Danio rerio) is emerging as a new important species for studying mechanisms of brain function and dysfunction. Focusing on selected central nervous system (CNS) disorders (brain cancer, epilepsy, and anxiety) and using them as examples, we discuss the value of zebrafish models in translational neuroscience. We further evaluate the contribution of zebrafish to neuroimaging, circuit level, and drug discovery research. Outlining the role of zebrafish in modeling a wide range of human brain disorders, we also summarize recent applications and existing challenges in this field. Finally, we emphasize the potential of zebrafish models in behavioral phenomics and high-throughput genetic/small molecule screening, which is critical for CNS drug discovery and identifying novel candidate genes. PMID:24726051

Systematic text condensation: a strategy for qualitative analysis.

PubMed

Malterud, Kirsti

2012-12-01

To present background, principles, and procedures for a strategy for qualitative analysis called systematic text condensation and discuss this approach compared with related strategies. Giorgi's psychological phenomenological analysis is the point of departure and inspiration for systematic text condensation. The basic elements of Giorgi's method and the elaboration of these in systematic text condensation are presented, followed by a detailed description of procedures for analysis according to systematic text condensation. Finally, similarities and differences compared with other frequently applied methods for qualitative analysis are identified, as the foundation of a discussion of strengths and limitations of systematic text condensation. Systematic text condensation is a descriptive and explorative method for thematic cross-case analysis of different types of qualitative data, such as interview studies, observational studies, and analysis of written texts. The method represents a pragmatic approach, although inspired by phenomenological ideas, and various theoretical frameworks can be applied. The procedure consists of the following steps: 1) total impression - from chaos to themes; 2) identifying and sorting meaning units - from themes to codes; 3) condensation - from code to meaning; 4) synthesizing - from condensation to descriptions and concepts. Similarities and differences comparing systematic text condensation with other frequently applied qualitative methods regarding thematic analysis, theoretical methodological framework, analysis procedures, and taxonomy are discussed. Systematic text condensation is a strategy for analysis developed from traditions shared by most of the methods for analysis of qualitative data. The method offers the novice researcher a process of intersubjectivity, reflexivity, and feasibility, while maintaining a responsible level of methodological rigour.

Combination of Metabolomic and Proteomic Analysis Revealed Different Features among Lactobacillus delbrueckii Subspecies bulgaricus and lactis Strains While In Vivo Testing in the Model Organism Caenorhabditis elegans Highlighted Probiotic Properties

PubMed Central

Zanni, Elena; Schifano, Emily; Motta, Sara; Sciubba, Fabio; Palleschi, Claudio; Mauri, Pierluigi; Perozzi, Giuditta; Uccelletti, Daniela; Devirgiliis, Chiara; Miccheli, Alfredo

2017-01-01

Lactobacillus delbrueckii represents a technologically relevant member of lactic acid bacteria, since the two subspecies bulgaricus and lactis are widely associated with fermented dairy products. In the present work, we report the characterization of two commercial strains belonging to L. delbrueckii subspecies bulgaricus, lactis and a novel strain previously isolated from a traditional fermented fresh cheese. A phenomic approach was performed by combining metabolomic and proteomic analysis of the three strains, which were subsequently supplemented as food source to the model organism Caenorhabditis elegans, with the final aim to evaluate their possible probiotic effects. Restriction analysis of 16S ribosomal DNA revealed that the novel foodborne strain belonged to L. delbrueckii subspecies lactis. Proteomic and metabolomic approaches showed differences in folate, aminoacid and sugar metabolic pathways among the three strains. Moreover, evaluation of C. elegans lifespan, larval development, brood size, and bacterial colonization capacity demonstrated that L. delbrueckii subsp. bulgaricus diet exerted beneficial effects on nematodes. On the other hand, both L. delbrueckii subsp. lactis strains affected lifespan and larval development. We have characterized three strains belonging to L. delbrueckii subspecies bulgaricus and lactis highlighting their divergent origin. In particular, the two closely related isolates L. delbrueckii subspecies lactis display different galactose metabolic capabilities. Moreover, the L. delbrueckii subspecies bulgaricus strain demonstrated potential probiotic features. Combination of omic platforms coupled with in vivo screening in the simple model organism C. elegans is a powerful tool to characterize industrially relevant bacterial isolates. PMID:28702021

Combination of Metabolomic and Proteomic Analysis Revealed Different Features among Lactobacillus delbrueckii Subspecies bulgaricus and lactis Strains While In Vivo Testing in the Model Organism Caenorhabditis elegans Highlighted Probiotic Properties.

PubMed

Zanni, Elena; Schifano, Emily; Motta, Sara; Sciubba, Fabio; Palleschi, Claudio; Mauri, Pierluigi; Perozzi, Giuditta; Uccelletti, Daniela; Devirgiliis, Chiara; Miccheli, Alfredo

2017-01-01

Lactobacillus delbrueckii represents a technologically relevant member of lactic acid bacteria, since the two subspecies bulgaricus and lactis are widely associated with fermented dairy products. In the present work, we report the characterization of two commercial strains belonging to L. delbrueckii subspecies bulgaricus , lactis and a novel strain previously isolated from a traditional fermented fresh cheese. A phenomic approach was performed by combining metabolomic and proteomic analysis of the three strains, which were subsequently supplemented as food source to the model organism Caenorhabditis elegans , with the final aim to evaluate their possible probiotic effects. Restriction analysis of 16S ribosomal DNA revealed that the novel foodborne strain belonged to L. delbrueckii subspecies lactis . Proteomic and metabolomic approaches showed differences in folate, aminoacid and sugar metabolic pathways among the three strains. Moreover, evaluation of C. elegans lifespan, larval development, brood size, and bacterial colonization capacity demonstrated that L. delbrueckii subsp. bulgaricus diet exerted beneficial effects on nematodes. On the other hand, both L. delbrueckii subsp. lactis strains affected lifespan and larval development. We have characterized three strains belonging to L. delbrueckii subspecies bulgaricus and lactis highlighting their divergent origin. In particular, the two closely related isolates L. delbrueckii subspecies lactis display different galactose metabolic capabilities. Moreover, the L. delbrueckii subspecies bulgaricus strain demonstrated potential probiotic features. Combination of omic platforms coupled with in vivo screening in the simple model organism C. elegans is a powerful tool to characterize industrially relevant bacterial isolates.

Integrative Analysis of Many Weighted Co-Expression Networks Using Tensor Computation

PubMed Central

Li, Wenyuan; Liu, Chun-Chi; Zhang, Tong; Li, Haifeng; Waterman, Michael S.; Zhou, Xianghong Jasmine

2011-01-01

The rapid accumulation of biological networks poses new challenges and calls for powerful integrative analysis tools. Most existing methods capable of simultaneously analyzing a large number of networks were primarily designed for unweighted networks, and cannot easily be extended to weighted networks. However, it is known that transforming weighted into unweighted networks by dichotomizing the edges of weighted networks with a threshold generally leads to information loss. We have developed a novel, tensor-based computational framework for mining recurrent heavy subgraphs in a large set of massive weighted networks. Specifically, we formulate the recurrent heavy subgraph identification problem as a heavy 3D subtensor discovery problem with sparse constraints. We describe an effective approach to solving this problem by designing a multi-stage, convex relaxation protocol, and a non-uniform edge sampling technique. We applied our method to 130 co-expression networks, and identified 11,394 recurrent heavy subgraphs, grouped into 2,810 families. We demonstrated that the identified subgraphs represent meaningful biological modules by validating against a large set of compiled biological knowledge bases. We also showed that the likelihood for a heavy subgraph to be meaningful increases significantly with its recurrence in multiple networks, highlighting the importance of the integrative approach to biological network analysis. Moreover, our approach based on weighted graphs detects many patterns that would be overlooked using unweighted graphs. In addition, we identified a large number of modules that occur predominately under specific phenotypes. This analysis resulted in a genome-wide mapping of gene network modules onto the phenome. Finally, by comparing module activities across many datasets, we discovered high-order dynamic cooperativeness in protein complex networks and transcriptional regulatory networks. PMID:21698123

Non-actual motion: phenomenological analysis and linguistic evidence.

PubMed

Blomberg, Johan; Zlatev, Jordan

2015-09-01

Sentences with motion verbs describing static situations have been seen as evidence that language and cognition are geared toward dynamism and change (Talmy in Toward a cognitive semantics, MIT Press, Cambridge, 2000; Langacker in Concept, image, and symbol: the cognitive basis of grammar, Mouton de Gruyter, Berlin and New York, 1990). Different concepts have been used in the literature, e.g., fictive motion, subjective motion and abstract motion to denote this. Based on phenomenological analysis, we reinterpret such concepts as reflecting different motivations for the use of such constructions (Blomberg and Zlatev in Phenom Cogn Sci 13(3):395-418, 2014). To highlight the multifaceted character of the phenomenon, we propose the concept non-actual motion (NAM), which we argue is more compatible with the situated cognition approach than explanations such as "mental simulation" (e.g., Matlock in Studies in linguistic motivation, Mouton de Gruyter, Berlin, 2004). We investigate the expression of NAM by means of a picture-based elicitation task with speakers of Swedish, French and Thai. Pictures represented figures that either afford human motion or not (±afford); crossed with this, the figure extended either across the picture from a third-person perspective (3 pp) or from a first-person perspective (1 pp). All picture types elicited NAM-sentences with the combination [+afford, 1 pp] producing most NAM-sentences in all three languages. NAM-descriptions also conformed to language-specific patterns for the expression of actual motion. We conclude that NAM shows interaction between pre-linguistic motivations and language-specific conventions.

Arabidopsis phenotyping through Geometric Morphometrics.

PubMed

Manacorda, Carlos A; Asurmendi, Sebastian

2018-06-18

Recently, much technical progress was achieved in the field of plant phenotyping. High-throughput platforms and the development of improved algorithms for rosette image segmentation make it now possible to extract shape and size parameters for genetic, physiological and environmental studies on a large scale. The development of low-cost phenotyping platforms and freeware resources make it possible to widely expand phenotypic analysis tools for Arabidopsis. However, objective descriptors of shape parameters that could be used independently of platform and segmentation software used are still lacking and shape descriptions still rely on ad hoc or even sometimes contradictory descriptors, which could make comparisons difficult and perhaps inaccurate. Modern geometric morphometrics is a family of methods in quantitative biology proposed to be the main source of data and analytical tools in the emerging field of phenomics studies. Based on the location of landmarks (corresponding points) over imaged specimens and by combining geometry, multivariate analysis and powerful statistical techniques, these tools offer the possibility to reproducibly and accurately account for shape variations amongst groups and measure them in shape distance units. Here, a particular scheme of landmarks placement on Arabidopsis rosette images is proposed to study shape variation in the case of viral infection processes. Shape differences between controls and infected plants are quantified throughout the infectious process and visualized. Quantitative comparisons between two unrelated ssRNA+ viruses are shown and reproducibility issues are assessed. Combined with the newest automated platforms and plant segmentation procedures, geometric morphometric tools could boost phenotypic features extraction and processing in an objective, reproducible manner.

Cellular responses during morphological transformation in Azospirillum brasilense and Its flcA knockout mutant.

PubMed

Hou, Xingsheng; McMillan, Mary; Coumans, Joëlle V F; Poljak, Anne; Raftery, Mark J; Pereg, Lily

2014-01-01

FlcA is a response regulator controlling flocculation and the morphological transformation of Azospirillum cells from vegetative to cyst-like forms. To understand the cellular responses of Azospirillum to conditions that cause morphological transformation, proteins differentially expressed under flocculation conditions in A. brasilense Sp7 and its flcA knockout mutant were investigated. Comparison of 2-DE protein profiles of wild-type (Sp7) and a flcA deletion mutant (Sp7-flcAΔ) revealed a total of 33 differentially expressed 2-DE gel spots, with 22 of these spots confidently separated to allow protein identification. Analysis of these spots by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and MASCOT database searching identified 48 proteins (≥10% emPAI in each spot). The functional characteristics of these proteins included carbon metabolism (beta-ketothiolase and citrate synthase), nitrogen metabolism (Glutamine synthetase and nitric oxide synthase), stress tolerance (superoxide dismutase, Alkyl hydroperoxidase and ATP-dependent Clp protease proteolytic subunit) and morphological transformation (transducer coupling protein). The observed differences between Sp7 wild-type and flcA- strains enhance our understanding of the morphological transformation process and help to explain previous phenotypical observations. This work is a step forward in connecting the Azospirillum phenome and genome.

Cellular Responses during Morphological Transformation in Azospirillum brasilense and Its flcA Knockout Mutant

PubMed Central

Coumans, Joëlle V. F.; Poljak, Anne; Raftery, Mark J.; Pereg, Lily

2014-01-01

FlcA is a response regulator controlling flocculation and the morphological transformation of Azospirillum cells from vegetative to cyst-like forms. To understand the cellular responses of Azospirillum to conditions that cause morphological transformation, proteins differentially expressed under flocculation conditions in A. brasilense Sp7 and its flcA knockout mutant were investigated. Comparison of 2-DE protein profiles of wild-type (Sp7) and a flcA deletion mutant (Sp7-flcAΔ) revealed a total of 33 differentially expressed 2-DE gel spots, with 22 of these spots confidently separated to allow protein identification. Analysis of these spots by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and MASCOT database searching identified 48 proteins (≥10% emPAI in each spot). The functional characteristics of these proteins included carbon metabolism (beta-ketothiolase and citrate synthase), nitrogen metabolism (Glutamine synthetase and nitric oxide synthase), stress tolerance (superoxide dismutase, Alkyl hydroperoxidase and ATP-dependent Clp protease proteolytic subunit) and morphological transformation (transducer coupling protein). The observed differences between Sp7 wild-type and flcA − strains enhance our understanding of the morphological transformation process and help to explain previous phenotypical observations. This work is a step forward in connecting the Azospirillum phenome and genome. PMID:25502569

Wine yeast phenomics: A standardized fermentation method for assessing quantitative traits of Saccharomyces cerevisiae strains in enological conditions.

PubMed

Peltier, Emilien; Bernard, Margaux; Trujillo, Marine; Prodhomme, Duyên; Barbe, Jean-Christophe; Gibon, Yves; Marullo, Philippe

2018-01-01

This work describes the set up of a small scale fermentation methodology for measuring quantitative traits of hundreds of samples in an enological context. By using standardized screw cap vessels, the alcoholic fermentation kinetics of Saccharomyces cerevisiae strains were measured by following their weight loss over the time. This dispositive was coupled with robotized enzymatic assays for measuring metabolites of enological interest in natural grape juices. Despite the small volume used, kinetic parameters and fermentation end products measured are similar with those observed in larger scale vats. The vessel used also offers the possibility to assay 32 volatiles compounds using a headspace solid-phase micro-extraction coupled to gas chromatography and mass spectrometry. The vessel shaking applied strongly impacted most of the phenotypes investigated due to oxygen transfer occuring in the first hours of the alcoholic fermentation. The impact of grape must and micro-oxygenation was investigated illustrating some relevant genetic x environmental interactions. By phenotyping a wide panel of commercial wine starters in five grape juices, broad phenotypic correlations between kinetics and metabolic end products were evidentiated. Moreover, a multivariate analysis illustrates that some grape musts are more able than others to discriminate commercial strains since some are less robust to environmental changes.

Phenomics allows identification of genomic regions affecting maize stomatal conductance with conditional effects of water deficit and evaporative demand.

PubMed

Prado, Santiago Alvarez; Cabrera-Bosquet, Llorenç; Grau, Antonin; Coupel-Ledru, Aude; Millet, Emilie J; Welcker, Claude; Tardieu, François

2018-02-01

Stomatal conductance is central for the trades-off between hydraulics and photosynthesis. We aimed at deciphering its genetic control and that of its responses to evaporative demand and water deficit, a nearly impossible task with gas exchanges measurements. Whole-plant stomatal conductance was estimated via inversion of the Penman-Monteith equation from data of transpiration and plant architecture collected in a phenotyping platform. We have analysed jointly 4 experiments with contrasting environmental conditions imposed to a panel of 254 maize hybrids. Estimated whole-plant stomatal conductance closely correlated with gas-exchange measurements and biomass accumulation rate. Sixteen robust quantitative trait loci (QTLs) were identified by genome wide association studies and co-located with QTLs of transpiration and biomass. Light, vapour pressure deficit, or soil water potential largely accounted for the differences in allelic effects between experiments, thereby providing strong hypotheses for mechanisms of stomatal control and a way to select relevant candidate genes among the 1-19 genes harboured by QTLs. The combination of allelic effects, as affected by environmental conditions, accounted for the variability of stomatal conductance across a range of hybrids and environmental conditions. This approach may therefore contribute to genetic analysis and prediction of stomatal control in diverse environments. © 2017 John Wiley & Sons Ltd.

Comparison of Leaf Sheath Transcriptome Profiles with Physiological Traits of Bread Wheat Cultivars under Salinity Stress

PubMed Central

Trittermann, Christine; Berger, Bettina; Roy, Stuart J.; Seki, Motoaki; Shinozaki, Kazuo; Tester, Mark

2015-01-01

Salinity stress has significant negative effects on plant biomass production and crop yield. Salinity tolerance is controlled by complex systems of gene expression and ion transport. The relationship between specific features of mild salinity stress adaptation and gene expression was analyzed using four commercial varieties of bread wheat (Triticum aestivum) that have different levels of salinity tolerance. The high-throughput phenotyping system in The Plant Accelerator at the Australian Plant Phenomics Facility revealed variation in shoot relative growth rate and salinity tolerance among the four cultivars. Comparative analysis of gene expression in the leaf sheaths identified genes whose functions are potentially linked to shoot biomass development and salinity tolerance. Early responses to mild salinity stress through changes in gene expression have an influence on the acquisition of stress tolerance and improvement in biomass accumulation during the early “osmotic” phase of salinity stress. In addition, results revealed transcript profiles for the wheat cultivars that were different from those of usual stress-inducible genes, but were related to those of plant growth. These findings suggest that, in the process of breeding, selection of specific traits with various salinity stress-inducible genes in commercial bread wheat has led to adaptation to mild salinity conditions. PMID:26244554

Wine yeast phenomics: A standardized fermentation method for assessing quantitative traits of Saccharomyces cerevisiae strains in enological conditions

PubMed Central

Bernard, Margaux; Trujillo, Marine; Prodhomme, Duyên; Barbe, Jean-Christophe; Gibon, Yves; Marullo, Philippe

2018-01-01

This work describes the set up of a small scale fermentation methodology for measuring quantitative traits of hundreds of samples in an enological context. By using standardized screw cap vessels, the alcoholic fermentation kinetics of Saccharomyces cerevisiae strains were measured by following their weight loss over the time. This dispositive was coupled with robotized enzymatic assays for measuring metabolites of enological interest in natural grape juices. Despite the small volume used, kinetic parameters and fermentation end products measured are similar with those observed in larger scale vats. The vessel used also offers the possibility to assay 32 volatiles compounds using a headspace solid-phase micro-extraction coupled to gas chromatography and mass spectrometry. The vessel shaking applied strongly impacted most of the phenotypes investigated due to oxygen transfer occuring in the first hours of the alcoholic fermentation. The impact of grape must and micro-oxygenation was investigated illustrating some relevant genetic x environmental interactions. By phenotyping a wide panel of commercial wine starters in five grape juices, broad phenotypic correlations between kinetics and metabolic end products were evidentiated. Moreover, a multivariate analysis illustrates that some grape musts are more able than others to discriminate commercial strains since some are less robust to environmental changes. PMID:29351285

Large-Scale Phenomics Identifies Primary and Fine-Tuning Roles for CRKs in Responses Related to Oxidative Stress

PubMed Central

Rayapuram, Channabasavangowda; Idänheimo, Niina; Hunter, Kerri; Kimura, Sachie; Merilo, Ebe; Vaattovaara, Aleksia; Oracz, Krystyna; Kaufholdt, David; Pallon, Andres; Anggoro, Damar Tri; Glów, Dawid; Lowe, Jennifer; Zhou, Ji; Mohammadi, Omid; Puukko, Tuomas; Albert, Andreas; Lang, Hans; Ernst, Dieter; Kollist, Hannes; Brosché, Mikael; Durner, Jörg; Borst, Jan Willem; Collinge, David B.; Karpiński, Stanisław; Lyngkjær, Michael F.; Robatzek, Silke; Wrzaczek, Michael; Kangasjärvi, Jaakko

2015-01-01

Cysteine-rich receptor-like kinases (CRKs) are transmembrane proteins characterized by the presence of two domains of unknown function 26 (DUF26) in their ectodomain. The CRKs form one of the largest groups of receptor-like protein kinases in plants, but their biological functions have so far remained largely uncharacterized. We conducted a large-scale phenotyping approach of a nearly complete crk T-DNA insertion line collection showing that CRKs control important aspects of plant development and stress adaptation in response to biotic and abiotic stimuli in a non-redundant fashion. In particular, the analysis of reactive oxygen species (ROS)-related stress responses, such as regulation of the stomatal aperture, suggests that CRKs participate in ROS/redox signalling and sensing. CRKs play general and fine-tuning roles in the regulation of stomatal closure induced by microbial and abiotic cues. Despite their great number and high similarity, large-scale phenotyping identified specific functions in diverse processes for many CRKs and indicated that CRK2 and CRK5 play predominant roles in growth regulation and stress adaptation, respectively. As a whole, the CRKs contribute to specificity in ROS signalling. Individual CRKs control distinct responses in an antagonistic fashion suggesting future potential for using CRKs in genetic approaches to improve plant performance and stress tolerance. PMID:26197346

Animal biometrics: quantifying and detecting phenotypic appearance.

PubMed

Kühl, Hjalmar S; Burghardt, Tilo

2013-07-01

Animal biometrics is an emerging field that develops quantified approaches for representing and detecting the phenotypic appearance of species, individuals, behaviors, and morphological traits. It operates at the intersection between pattern recognition, ecology, and information sciences, producing computerized systems for phenotypic measurement and interpretation. Animal biometrics can benefit a wide range of disciplines, including biogeography, population ecology, and behavioral research. Currently, real-world applications are gaining momentum, augmenting the quantity and quality of ecological data collection and processing. However, to advance animal biometrics will require integration of methodologies among the scientific disciplines involved. Such efforts will be worthwhile because the great potential of this approach rests with the formal abstraction of phenomics, to create tractable interfaces between different organizational levels of life. Copyright © 2013 Elsevier Ltd. All rights reserved.

Human genetics: international projects and personalized medicine.

PubMed

Apellaniz-Ruiz, Maria; Gallego, Cristina; Ruiz-Pinto, Sara; Carracedo, Angel; Rodríguez-Antona, Cristina

2016-03-01

In this article, we present the progress driven by the recent technological advances and new revolutionary massive sequencing technologies in the field of human genetics. We discuss this knowledge in relation with drug response prediction, from the germline genetic variation compiled in the 1000 Genomes Project or in the Genotype-Tissue Expression project, to the phenome-genome archives, the international cancer projects, such as The Cancer Genome Atlas or the International Cancer Genome Consortium, and the epigenetic variation and its influence in gene expression, including the regulation of drug metabolism. This review is based on the lectures presented by the speakers of the Symposium "Human Genetics: International Projects & New Technologies" from the VII Conference of the Spanish Pharmacogenetics and Pharmacogenomics Society, held on the 20th and 21st of April 2015.

Phenome-Wide Association Study (PheWAS) for Detection of Pleiotropy within the Population Architecture using Genomics and Epidemiology (PAGE) Network

PubMed Central

Pendergrass, Sarah A.; Brown-Gentry, Kristin; Dudek, Scott; Frase, Alex; Torstenson, Eric S.; Goodloe, Robert; Ambite, Jose Luis; Avery, Christy L.; Buyske, Steve; Bůžková, Petra; Deelman, Ewa; Fesinmeyer, Megan D.; Haiman, Christopher A.; Heiss, Gerardo; Hindorff, Lucia A.; Hsu, Chu-Nan; Jackson, Rebecca D.; Kooperberg, Charles; Le Marchand, Loic; Lin, Yi; Matise, Tara C.; Monroe, Kristine R.; Moreland, Larry; Park, Sungshim L.; Reiner, Alex; Wallace, Robert; Wilkens, Lynn R.; Crawford, Dana C.; Ritchie, Marylyn D.

2013-01-01

Using a phenome-wide association study (PheWAS) approach, we comprehensively tested genetic variants for association with phenotypes available for 70,061 study participants in the Population Architecture using Genomics and Epidemiology (PAGE) network. Our aim was to better characterize the genetic architecture of complex traits and identify novel pleiotropic relationships. This PheWAS drew on five population-based studies representing four major racial/ethnic groups (European Americans (EA), African Americans (AA), Hispanics/Mexican-Americans, and Asian/Pacific Islanders) in PAGE, each site with measurements for multiple traits, associated laboratory measures, and intermediate biomarkers. A total of 83 single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) were genotyped across two or more PAGE study sites. Comprehensive tests of association, stratified by race/ethnicity, were performed, encompassing 4,706 phenotypes mapped to 105 phenotype-classes, and association results were compared across study sites. A total of 111 PheWAS results had significant associations for two or more PAGE study sites with consistent direction of effect with a significance threshold of p<0.01 for the same racial/ethnic group, SNP, and phenotype-class. Among results identified for SNPs previously associated with phenotypes such as lipid traits, type 2 diabetes, and body mass index, 52 replicated previously published genotype–phenotype associations, 26 represented phenotypes closely related to previously known genotype–phenotype associations, and 33 represented potentially novel genotype–phenotype associations with pleiotropic effects. The majority of the potentially novel results were for single PheWAS phenotype-classes, for example, for CDKN2A/B rs1333049 (previously associated with type 2 diabetes in EA) a PheWAS association was identified for hemoglobin levels in AA. Of note, however, GALNT2 rs2144300 (previously associated with high-density lipoprotein cholesterol levels in EA) had multiple potentially novel PheWAS associations, with hypertension related phenotypes in AA and with serum calcium levels and coronary artery disease phenotypes in EA. PheWAS identifies associations for hypothesis generation and exploration of the genetic architecture of complex traits. PMID:23382687

Evaluation of Borage Extracts As Potential Biostimulant Using a Phenomic, Agronomic, Physiological, and Biochemical Approach.

PubMed

Bulgari, Roberta; Morgutti, Silvia; Cocetta, Giacomo; Negrini, Noemi; Farris, Stefano; Calcante, Aldo; Spinardi, Anna; Ferrari, Enrico; Mignani, Ilaria; Oberti, Roberto; Ferrante, Antonio

2017-01-01

Biostimulants are substances able to improve water and nutrient use efficiency and counteract stress factors by enhancing primary and secondary metabolism. Premise of the work was to exploit raw extracts from leaves (LE) or flowers (FE) of Borago officinalis L., to enhance yield and quality of Lactuca sativa 'Longifolia,' and to set up a protocol to assess their effects. To this aim, an integrated study on agronomic, physiological and biochemical aspects, including also a phenomic approach, has been adopted. Extracts were diluted to 1 or 10 mL L -1 , sprayed onto lettuce plants at the middle of the growing cycle and 1 day before harvest. Control plants were treated with water. Non-destructive analyses were conducted to assess the effect of extracts on biomass with an innovative imaging technique, and on leaf photosynthetic efficiency (chlorophyll a fluorescence and leaf gas exchanges). At harvest, the levels of ethylene, photosynthetic pigments, nitrate, and primary (sucrose and total sugars) and secondary (total phenols and flavonoids) metabolites, including the activity and levels of phenylalanine ammonia lyase (PAL) were assessed. Moreover, a preliminary study of the effects during postharvest was performed. Borage extracts enhanced the primary metabolism by increasing leaf pigments and photosynthetic activity. Plant fresh weight increased upon treatments with 10 mL L -1 doses, as correctly estimated by multi-view angles images. Chlorophyll a fluorescence data showed that FEs were able to increase the number of active reaction centers per cross section; a similar trend was observed for the performance index. Ethylene was three-fold lower in FEs treatments. Nitrate and sugar levels did not change in response to the different treatments. Total flavonoids and phenols, as well as the total protein levels, the in vitro PAL specific activity, and the levels of PAL-like polypeptides were increased by all borage extracts, with particular regard to FEs. FEs also proved efficient in preventing degradation and inducing an increase in photosynthetic pigments during storage. In conclusion, borage extracts, with particular regard to the flower ones, appear to indeed exert biostimulant effects on lettuce; future work will be required to further investigate on their efficacy in different conditions and/or species.

Detection of pleiotropy through a Phenome-wide association study (PheWAS) of epidemiologic data as part of the Environmental Architecture for Genes Linked to Environment (EAGLE) study.

PubMed

Hall, Molly A; Verma, Anurag; Brown-Gentry, Kristin D; Goodloe, Robert; Boston, Jonathan; Wilson, Sarah; McClellan, Bob; Sutcliffe, Cara; Dilks, Holly H; Gillani, Nila B; Jin, Hailing; Mayo, Ping; Allen, Melissa; Schnetz-Boutaud, Nathalie; Crawford, Dana C; Ritchie, Marylyn D; Pendergrass, Sarah A

2014-12-01

We performed a Phenome-wide association study (PheWAS) utilizing diverse genotypic and phenotypic data existing across multiple populations in the National Health and Nutrition Examination Surveys (NHANES), conducted by the Centers for Disease Control and Prevention (CDC), and accessed by the Epidemiological Architecture for Genes Linked to Environment (EAGLE) study. We calculated comprehensive tests of association in Genetic NHANES using 80 SNPs and 1,008 phenotypes (grouped into 184 phenotype classes), stratified by race-ethnicity. Genetic NHANES includes three surveys (NHANES III, 1999-2000, and 2001-2002) and three race-ethnicities: non-Hispanic whites (n = 6,634), non-Hispanic blacks (n = 3,458), and Mexican Americans (n = 3,950). We identified 69 PheWAS associations replicating across surveys for the same SNP, phenotype-class, direction of effect, and race-ethnicity at p<0.01, allele frequency >0.01, and sample size >200. Of these 69 PheWAS associations, 39 replicated previously reported SNP-phenotype associations, 9 were related to previously reported associations, and 21 were novel associations. Fourteen results had the same direction of effect across more than one race-ethnicity: one result was novel, 11 replicated previously reported associations, and two were related to previously reported results. Thirteen SNPs showed evidence of pleiotropy. We further explored results with gene-based biological networks, contrasting the direction of effect for pleiotropic associations across phenotypes. One PheWAS result was ABCG2 missense SNP rs2231142, associated with uric acid levels in both non-Hispanic whites and Mexican Americans, protoporphyrin levels in non-Hispanic whites and Mexican Americans, and blood pressure levels in Mexican Americans. Another example was SNP rs1800588 near LIPC, significantly associated with the novel phenotypes of folate levels (Mexican Americans), vitamin E levels (non-Hispanic whites) and triglyceride levels (non-Hispanic whites), and replication for cholesterol levels. The results of this PheWAS show the utility of this approach for exposing more of the complex genetic architecture underlying multiple traits, through generating novel hypotheses for future research.

Sarcoidosis Related Novel Candidate Genes Identified by Multi-Omics Integrative Analyses.

PubMed

Hočevar, Keli; Maver, Aleš; Kunej, Tanja; Peterlin, Borut

2018-05-01

Sarcoidosis is a multifactorial systemic disease characterized by granulomatous inflammation and greatly impacting on global public health. The etiology and mechanisms of sarcoidosis are not fully understood. Recent high-throughput biological research has generated vast amounts of multi-omics big data on sarcoidosis, but their significance remains to be determined. We sought to identify novel candidate regions, and genes consistently altered in heterogeneous omics studies so as to reveal the underlying molecular mechanisms. We conducted a comprehensive integrative literature analysis on global data on sarcoidosis, including genomic, transcriptomic, proteomic, and phenomic studies. We performed positional integration analysis of 38 eligible datasets originating from 17 different biological layers. Using the integration interval length of 50 kb, we identified 54 regions reaching significance value p ≤ 0.0001 and 15 regions with significance value p ≤ 0.00001, when applying more stringent criteria. Secondary literature analysis of the top 20 regions, with the most significant accumulation of signals, revealed several novel candidate genes for which associations with sarcoidosis have not yet been established, but have considerable support for their involvement based on omic data. These new plausible candidate genes include NELFE, CFB, EGFL7, AGPAT2, FKBPL, NRC3, and NEU1. Furthermore, annotated data were prepared to enable custom visualization and browsing of these sarcoidosis related omics evidence in the University of California Santa Cruz (UCSC) Genome Browser. Further multi-omics approaches are called for sarcoidosis biomarkers and diagnostic and therapeutic innovation. Our approach for harnessing multi-omics data and the findings presented herein reflect important steps toward understanding the etiology and underlying pathological mechanisms of sarcoidosis.

Germline PARP4 mutations in patients with primary thyroid and breast cancers.

PubMed

Ikeda, Yuji; Kiyotani, Kazuma; Yew, Poh Yin; Kato, Taigo; Tamura, Kenji; Yap, Kai Lee; Nielsen, Sarah M; Mester, Jessica L; Eng, Charis; Nakamura, Yusuke; Grogan, Raymon H

2016-03-01

Germline mutations in the PTEN gene, which cause Cowden syndrome, are known to be one of the genetic factors for primary thyroid and breast cancers; however, PTEN mutations are found in only a small subset of research participants with non-syndrome breast and thyroid cancers. In this study, we aimed to identify germline variants that may be related to genetic risk of primary thyroid and breast cancers. Genomic DNAs extracted from peripheral blood of 14 PTEN WT female research participants with primary thyroid and breast cancers were analyzed by whole-exome sequencing. Gene-based case-control association analysis using the information of 406 Europeans obtained from the 1000 Genomes Project database identified 34 genes possibly associated with the phenotype with P < 1.0 × 10(-3). Among them, rare variants in the PARP4 gene were detected at significant high frequency (odds ratio = 5.2; P = 1.0 × 10(-5)). The variants, G496V and T1170I, were found in six of the 14 study participants (43%) while their frequencies were only 0.5% in controls. Functional analysis using HCC1143 cell line showed that knockdown of PARP4 with siRNA significantly enhanced the cell proliferation, compared with the cells transfected with siControl (P = 0.02). Kaplan-Meier analysis using Gene Expression Omnibus (GEO), European Genome-phenome Archive (EGA) and The Cancer Genome Atlas (TCGA) datasets showed poor relapse-free survival (P < 0.001, Hazard ratio 1.27) and overall survival (P = 0.006, Hazard ratio 1.41) in a PARP4 low-expression group, suggesting that PARP4 may function as a tumor suppressor. In conclusion, we identified PARP4 as a possible susceptibility gene of primary thyroid and breast cancer. © 2016 Society for Endocrinology.

Utilization of a high-throughput shoot imaging system to examine the dynamic phenotypic responses of a C4 cereal crop plant to nitrogen and water deficiency over time

PubMed Central

Neilson, E. H.; Edwards, A. M.; Blomstedt, C. K.; Berger, B.; Møller, B. Lindberg; Gleadow, R. M.

2015-01-01

The use of high-throughput phenotyping systems and non-destructive imaging is widely regarded as a key technology allowing scientists and breeders to develop crops with the ability to perform well under diverse environmental conditions. However, many of these phenotyping studies have been optimized using the model plant Arabidopsis thaliana. In this study, The Plant Accelerator® at The University of Adelaide, Australia, was used to investigate the growth and phenotypic response of the important cereal crop, Sorghum bicolor L. Moench and related hybrids to water-limited conditions and different levels of fertilizer. Imaging in different spectral ranges was used to monitor plant composition, chlorophyll, and moisture content. Phenotypic image analysis accurately measured plant biomass. The data set obtained enabled the responses of the different sorghum varieties to the experimental treatments to be differentiated and modelled. Plant architectural instead of architecture elements were determined using imaging and found to correlate with an improved tolerance to stress, for example diurnal leaf curling and leaf area index. Analysis of colour images revealed that leaf ‘greenness’ correlated with foliar nitrogen and chlorophyll, while near infrared reflectance (NIR) analysis was a good predictor of water content and leaf thickness, and correlated with plant moisture content. It is shown that imaging sorghum using a high-throughput system can accurately identify and differentiate between growth and specific phenotypic traits. R scripts for robust, parsimonious models are provided to allow other users of phenomic imaging systems to extract useful data readily, and thus relieve a bottleneck in phenotypic screening of multiple genotypes of key crop plants. PMID:25697789

Resources and Recommendations for Using Transcriptomics to Address Grand Challenges in Comparative Biology.

PubMed

Mykles, Donald L; Burnett, Karen G; Durica, David S; Joyce, Blake L; McCarthy, Fiona M; Schmidt, Carl J; Stillman, Jonathon H

2016-12-01

High-throughput RNA sequencing (RNA-seq) technology has become an important tool for studying physiological responses of organisms to changes in their environment. De novo assembly of RNA-seq data has allowed researchers to create a comprehensive catalog of genes expressed in a tissue and to quantify their expression without a complete genome sequence. The contributions from the "Tapping the Power of Crustacean Transcriptomics to Address Grand Challenges in Comparative Biology" symposium in this issue show the successes and limitations of using RNA-seq in the study of crustaceans. In conjunction with the symposium, the Animal Genome to Phenome Research Coordination Network collated comments from participants at the meeting regarding the challenges encountered when using transcriptomics in their research. Input came from novices and experts ranging from graduate students to principal investigators. Many were unaware of the bioinformatics analysis resources currently available on the CyVerse platform. Our analysis of community responses led to three recommendations for advancing the field: (1) integration of genomic and RNA-seq sequence assemblies for crustacean gene annotation and comparative expression; (2) development of methodologies for the functional analysis of genes; and (3) information and training exchange among laboratories for transmission of best practices. The field lacks the methods for manipulating tissue-specific gene expression. The decapod crustacean research community should consider the cherry shrimp, Neocaridina denticulata, as a decapod model for the application of transgenic tools for functional genomics. This would require a multi-investigator effort. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Integration of EGA secure data access into Galaxy.

PubMed

Hoogstrate, Youri; Zhang, Chao; Senf, Alexander; Bijlard, Jochem; Hiltemann, Saskia; van Enckevort, David; Repo, Susanna; Heringa, Jaap; Jenster, Guido; J A Fijneman, Remond; Boiten, Jan-Willem; A Meijer, Gerrit; Stubbs, Andrew; Rambla, Jordi; Spalding, Dylan; Abeln, Sanne

2016-01-01

High-throughput molecular profiling techniques are routinely generating vast amounts of data for translational medicine studies. Secure access controlled systems are needed to manage, store, transfer and distribute these data due to its personally identifiable nature. The European Genome-phenome Archive (EGA) was created to facilitate access and management to long-term archival of bio-molecular data. Each data provider is responsible for ensuring a Data Access Committee is in place to grant access to data stored in the EGA. Moreover, the transfer of data during upload and download is encrypted. ELIXIR, a European research infrastructure for life-science data, initiated a project (2016 Human Data Implementation Study) to understand and document the ELIXIR requirements for secure management of controlled-access data. As part of this project, a full ecosystem was designed to connect archived raw experimental molecular profiling data with interpreted data and the computational workflows, using the CTMM Translational Research IT (CTMM-TraIT) infrastructure http://www.ctmm-trait.nl as an example. Here we present the first outcomes of this project, a framework to enable the download of EGA data to a Galaxy server in a secure way. Galaxy provides an intuitive user interface for molecular biologists and bioinformaticians to run and design data analysis workflows. More specifically, we developed a tool -- ega_download_streamer - that can download data securely from EGA into a Galaxy server, which can subsequently be further processed. This tool will allow a user within the browser to run an entire analysis containing sensitive data from EGA, and to make this analysis available for other researchers in a reproducible manner, as shown with a proof of concept study.  The tool ega_download_streamer is available in the Galaxy tool shed: https://toolshed.g2.bx.psu.edu/view/yhoogstrate/ega_download_streamer.

Integration of EGA secure data access into Galaxy

PubMed Central

Hoogstrate, Youri; Zhang, Chao; Senf, Alexander; Bijlard, Jochem; Hiltemann, Saskia; van Enckevort, David; Repo, Susanna; Heringa, Jaap; Jenster, Guido; Fijneman, Remond J.A.; Boiten, Jan-Willem; A. Meijer, Gerrit; Stubbs, Andrew; Rambla, Jordi; Spalding, Dylan; Abeln, Sanne

2016-01-01

High-throughput molecular profiling techniques are routinely generating vast amounts of data for translational medicine studies. Secure access controlled systems are needed to manage, store, transfer and distribute these data due to its personally identifiable nature. The European Genome-phenome Archive (EGA) was created to facilitate access and management to long-term archival of bio-molecular data. Each data provider is responsible for ensuring a Data Access Committee is in place to grant access to data stored in the EGA. Moreover, the transfer of data during upload and download is encrypted. ELIXIR, a European research infrastructure for life-science data, initiated a project (2016 Human Data Implementation Study) to understand and document the ELIXIR requirements for secure management of controlled-access data. As part of this project, a full ecosystem was designed to connect archived raw experimental molecular profiling data with interpreted data and the computational workflows, using the CTMM Translational Research IT (CTMM-TraIT) infrastructure http://www.ctmm-trait.nl as an example. Here we present the first outcomes of this project, a framework to enable the download of EGA data to a Galaxy server in a secure way. Galaxy provides an intuitive user interface for molecular biologists and bioinformaticians to run and design data analysis workflows. More specifically, we developed a tool -- ega_download_streamer - that can download data securely from EGA into a Galaxy server, which can subsequently be further processed. This tool will allow a user within the browser to run an entire analysis containing sensitive data from EGA, and to make this analysis available for other researchers in a reproducible manner, as shown with a proof of concept study.  The tool ega_download_streamer is available in the Galaxy tool shed: https://toolshed.g2.bx.psu.edu/view/yhoogstrate/ega_download_streamer. PMID:28232859

Consistency and accuracy of indexing systematic review articles and meta-analyses in medline.

PubMed

Wilczynski, Nancy L; Haynes, R Brian

2009-09-01

Systematic review articles support the advance of science and translation of research evidence into healthcare practice. Inaccurate retrieval from medline could limit access to reviews. To determine the quality of indexing systematic reviews and meta-analyses in medline. The Clinical Hedges Database, containing the results of a hand search of 161 journals, was used to test medline indexing terms for their ability to retrieve systematic reviews that met predefined methodologic criteria (labelled as 'pass' review articles) and reviews that reported a meta-analysis. The Clinical Hedges Database contained 49 028 articles; 753 were 'pass' review articles (552 with a meta-analysis). In total 758 review articles (independent of whether they passed) reported a meta-analysis. The search strategy that retrieved the highest number of 'pass' systematic reviews achieved a sensitivity of 97.1%. The publication type 'meta analysis' had a false positive rate of 5.6% (95% CI 3.9 to 7.6), and false negative rate of 0.31% (95% CI 0.26 to 0.36) for retrieving systematic reviews that reported a meta-analysis. Inaccuracies in indexing systematic reviews and meta-analyses in medline can be partly overcome by a 5-term search strategy. Introducing a publication type for systematic reviews of the literature could improve retrieval performance.

Biological findings from the PheWAS catalog: focus on connective tissue-related disorders (pelvic floor dysfunction, abdominal hernia, varicose veins and hemorrhoids).

PubMed

Salnikova, Lyubov E; Khadzhieva, Maryam B; Kolobkov, Dmitry S

2016-07-01

Pelvic floor dysfunction, specifically genital prolapse (GP) and stress urinary inconsistency (SUI) presumably co-occur with other connective tissue disorders such as hernia, hemorrhoids, and varicose veins. Observations on non-random coexistence of these disorders have never been summarized in a meta-analysis. The performed meta-analysis demonstrated that varicose veins and hernia are associated with GP. Disease connections on the molecular level may be partially based on shared genetic susceptibility. A unique opportunity to estimate shared genetic susceptibility to disorders is provided by a PheWAS (phenome-wide association study) designed to utilize GWAS data concurrently to many phenotypes. We searched the PheWAS Catalog, which includes the results of the PheWAS study with P value < 0.05, for genes associated with GP, SUI, abdominal hernia, varicose veins and hemorrhoids. We found pronounced signals for the associations of the SLC2A9 gene with SUI (P = 6.0e-05) and the MYH9 gene with varicose veins of lower extremity (P = 0.0001) and hemorrhoids (P = 0.0007). The comparison of the PheWAS Catalog and the NHGRI Catalog data revealed enrichment of genes associated with bone mineral density in GP and with activated partial thromboplastin time in varicose veins of lower extremity. In cross-phenotype associations, genes responsible for peripheral nerve functions seem to predominate. This study not only established novel biologically plausible associations that may warrant further studies but also exemplified an effective use of the PheWAS Catalog data.

An integrated phenomic approach to multivariate allelic association

PubMed Central

Medland, Sarah Elizabeth; Neale, Michael Churton

2010-01-01

The increased feasibility of genome-wide association has resulted in association becoming the primary method used to localize genetic variants that cause phenotypic variation. Much attention has been focused on the vast multiple testing problems arising from analyzing large numbers of single nucleotide polymorphisms. However, the inflation of experiment-wise type I error rates through testing numerous phenotypes has received less attention. Multivariate analyses can be used to detect both pleiotropic effects that influence a latent common factor, and monotropic effects that operate at a variable-specific levels, whilst controlling for non-independence between phenotypes. In this study, we present a maximum likelihood approach, which combines both latent and variable-specific tests and which may be used with either individual or family data. Simulation results indicate that in the presence of factor-level association, the combined multivariate (CMV) analysis approach performs well with a minimal loss of power as compared with a univariate analysis of a factor or sum score (SS). As the deviation between the pattern of allelic effects and the factor loadings increases, the power of univariate analyses of both factor and SSs decreases dramatically, whereas the power of the CMV approach is maintained. We show the utility of the approach by examining the association between dopamine receptor D2 TaqIA and the initiation of marijuana, tranquilizers and stimulants in data from the Add Health Study. Perl scripts that takes ped and dat files as input and produces Mx scripts and data for running the CMV approach can be downloaded from www.vipbg.vcu.edu/~sarahme/WriteMx. PMID:19707246

A clinically driven variant prioritization framework outperforms purely computational approaches for the diagnostic analysis of singleton WES data.

PubMed

Stark, Zornitza; Dashnow, Harriet; Lunke, Sebastian; Tan, Tiong Y; Yeung, Alison; Sadedin, Simon; Thorne, Natalie; Macciocca, Ivan; Gaff, Clara; Oshlack, Alicia; White, Susan M; James, Paul A

2017-11-01

Rapid identification of clinically significant variants is key to the successful application of next generation sequencing technologies in clinical practice. The Melbourne Genomics Health Alliance (MGHA) variant prioritization framework employs a gene prioritization index based on clinician-generated a priori gene lists, and a variant prioritization index (VPI) based on rarity, conservation and protein effect. We used data from 80 patients who underwent singleton whole exome sequencing (WES) to test the ability of the framework to rank causative variants highly, and compared it against the performance of other gene and variant prioritization tools. Causative variants were identified in 59 of the patients. Using the MGHA prioritization framework the average rank of the causative variant was 2.24, with 76% ranked as the top priority variant, and 90% ranked within the top five. Using clinician-generated gene lists resulted in ranking causative variants an average of 8.2 positions higher than prioritization based on variant properties alone. This clinically driven prioritization approach significantly outperformed purely computational tools, placing a greater proportion of causative variants top or in the top 5 (permutation P-value=0.001). Clinicians included 40 of the 49 WES diagnoses in their a priori list of differential diagnoses (81%). The lists generated by PhenoTips and Phenomizer contained 14 (29%) and 18 (37%) of these diagnoses respectively. These results highlight the benefits of clinically led variant prioritization in increasing the efficiency of singleton WES data analysis and have important implications for developing models for the funding and delivery of genomic services.

Symmetry-plane model of 3D Euler flows: Mapping to regular systems and numerical solutions of blowup

NASA Astrophysics Data System (ADS)

Mulungye, Rachel M.; Lucas, Dan; Bustamante, Miguel D.

2014-11-01

We introduce a family of 2D models describing the dynamics on the so-called symmetry plane of the full 3D Euler fluid equations. These models depend on a free real parameter and can be solved analytically. For selected representative values of the free parameter, we apply the method introduced in [M.D. Bustamante, Physica D: Nonlinear Phenom. 240, 1092 (2011)] to map the fluid equations bijectively to globally regular systems. By comparing the analytical solutions with the results of numerical simulations, we establish that the numerical simulations of the mapped regular systems are far more accurate than the numerical simulations of the original systems, at the same spatial resolution and CPU time. In particular, the numerical integrations of the mapped regular systems produce robust estimates for the growth exponent and singularity time of the main blowup quantity (vorticity stretching rate), converging well to the analytically-predicted values even beyond the time at which the flow becomes under-resolved (i.e. the reliability time). In contrast, direct numerical integrations of the original systems develop unstable oscillations near the reliability time. We discuss the reasons for this improvement in accuracy, and explain how to extend the analysis to the full 3D case. Supported under the programme for Research in Third Level Institutions (PRTLI) Cycle 5 and co-funded by the European Regional Development Fund.

The human-induced pluripotent stem cell initiative—data resources for cellular genetics

PubMed Central

Streeter, Ian; Harrison, Peter W.; Faulconbridge, Adam; Flicek, Paul; Parkinson, Helen; Clarke, Laura

2017-01-01

The Human Induced Pluripotent Stem Cell Initiative (HipSci) isf establishing a large catalogue of human iPSC lines, arguably the most well characterized collection to date. The HipSci portal enables researchers to choose the right cell line for their experiment, and makes HipSci's rich catalogue of assay data easy to discover and reuse. Each cell line has genomic, transcriptomic, proteomic and cellular phenotyping data. Data are deposited in the appropriate EMBL-EBI archives, including the European Nucleotide Archive (ENA), European Genome-phenome Archive (EGA), ArrayExpress and PRoteomics IDEntifications (PRIDE) databases. The project will make 500 cell lines from healthy individuals, and from 150 patients with rare genetic diseases; these will be available through the European Collection of Authenticated Cell Cultures (ECACC). As of August 2016, 238 cell lines are available for purchase. Project data is presented through the HipSci data portal (http://www.hipsci.org/lines) and is downloadable from the associated FTP site (ftp://ftp.hipsci.ebi.ac.uk/vol1/ftp). The data portal presents a summary matrix of the HipSci cell lines, showing available data types. Each line has its own page containing descriptive metadata, quality information, and links to archived assay data. Analysis results are also available in a Track Hub, allowing visualization in the context of public genomic annotations (http://www.hipsci.org/data/trackhubs). PMID:27733501

Homozygosity mapping and sequencing identify two genes that might contribute to pointing behavior in hunting dogs.

PubMed

Akkad, Denis A; Gerding, Wanda M; Gasser, Robin B; Epplen, Jörg T

2015-01-01

The domestic dog represents an important model for studying the genetics of behavior. In spite of technological advances in genomics and phenomics, the genetic basis of most specific canine behaviors is largely unknown. Some breeds of hunting dogs exhibit a behavioral trait called "pointing" (a prolonged halt of movement to indicate the position of a game animal). Here, the genomes of pointing dogs (Large Munsterlander and Weimaraner) were compared with those of behaviorally distinct herding dogs (Berger des Pyrenées and Schapendoes). We assumed (i) that these four dog breeds initially represented inbred populations and (ii) that selective breeding for pointing behavior promotes an enrichment of the genetic trait in a homozygous state. The homozygosity mapping of 52 dogs (13 of each of the four breeds) followed by subsequent interval resequencing identified fixed genetic differences on chromosome 22 between pointers and herding dogs. In addition, we identified one non-synonomous variation in each of the coding genes SETDB2 and CYSLTR2 that might have a functional consequence. Genetic analysis of additional hunting and non-hunting dogs revealed consistent homozygosity for these two variations in six of seven pointing breeds. Based on the present findings, we propose that, together with other genetic, training and/or environmental factors, the nucleotide and associated amino acid variations identified in genes SETDB2 and CYSLTR2 contribute to pointing behavior.

Expanding the phenome and variome of skeletal dysplasia.

PubMed

Maddirevula, Sateesh; Alsahli, Saud; Alhabeeb, Lamees; Patel, Nisha; Alzahrani, Fatema; Shamseldin, Hanan E; Anazi, Shams; Ewida, Nour; Alsaif, Hessa S; Mohamed, Jawahir Y; Alazami, Anas M; Ibrahim, Niema; Abdulwahab, Firdous; Hashem, Mais; Abouelhoda, Mohamed; Monies, Dorota; Al Tassan, Nada; Alshammari, Muneera; Alsagheir, Afaf; Seidahmed, Mohammed Zain; Sogati, Samira; Aglan, Mona S; Hamad, Muddathir H; Salih, Mustafa A; Hamed, Ahlam A; Alhashmi, Nadia; Nabil, Amira; Alfadli, Fatima; Abdel-Salam, Ghada M H; Alkuraya, Hisham; Peitee, Winnie Ong; Keng, W T; Qasem, Abdullah; Mushiba, Aziza M; Zaki, Maha S; Fassad, Mahmoud R; Alfadhel, Majid; Alexander, Saji; Sabr, Yasser; Temtamy, Samia; Ekbote, Alka V; Ismail, Samira; Hosny, Gamal Ahmed; Otaify, Ghada A; Amr, Khalda; Al Tala, Saeed; Khan, Arif O; Rizk, Tamer; Alaqeel, Aida; Alsiddiky, Abdulmonem; Singh, Ankur; Kapoor, Seema; Alhashem, Amal; Faqeih, Eissa; Shaheen, Ranad; Alkuraya, Fowzan S

2018-04-05

PurposeTo describe our experience with a large cohort (411 patients from 288 families) of various forms of skeletal dysplasia who were molecularly characterized.MethodsDetailed phenotyping and next-generation sequencing (panel and exome).ResultsOur analysis revealed 224 pathogenic/likely pathogenic variants (54 (24%) of which are novel) in 123 genes with established or tentative links to skeletal dysplasia. In addition, we propose 5 genes as candidate disease genes with suggestive biological links (WNT3A, SUCO, RIN1, DIP2C, and PAN2). Phenotypically, we note that our cohort spans 36 established phenotypic categories by the International Skeletal Dysplasia Nosology, as well as 18 novel skeletal dysplasia phenotypes that could not be classified under these categories, e.g., the novel C3orf17-related skeletal dysplasia. We also describe novel phenotypic aspects of well-known disease genes, e.g., PGAP3-related Toriello-Carey syndrome-like phenotype. We note a strong founder effect for many genes in our cohort, which allowed us to calculate a minimum disease burden for the autosomal recessive forms of skeletal dysplasia in our population (7.16E-04), which is much higher than the global average.ConclusionBy expanding the phenotypic, allelic, and locus heterogeneity of skeletal dysplasia in humans, we hope our study will improve the diagnostic rate of patients with these conditions.GENETICS in MEDICINE advance online publication, 5 April 2018; doi:10.1038/gim.2018.50.

Integrating Image-Based Phenomics and Association Analysis to Dissect the Genetic Architecture of Temporal Salinity Responses in Rice1[OPEN

PubMed Central

Knecht, Avi C.; Wang, Dong

2015-01-01

Salinity affects a significant portion of arable land and is particularly detrimental for irrigated agriculture, which provides one-third of the global food supply. Rice (Oryza sativa), the most important food crop, is salt sensitive. The genetic resources for salt tolerance in rice germplasm exist but are underutilized due to the difficulty in capturing the dynamic nature of physiological responses to salt stress. The genetic basis of these physiological responses is predicted to be polygenic. In an effort to address this challenge, we generated temporal imaging data from 378 diverse rice genotypes across 14 d of 90 mm NaCl stress and developed a statistical model to assess the genetic architecture of dynamic salinity-induced growth responses in rice germplasm. A genomic region on chromosome 3 was strongly associated with the early growth response and was captured using visible range imaging. Fluorescence imaging identified four genomic regions linked to salinity-induced fluorescence responses. A region on chromosome 1 regulates both the fluorescence shift indicative of the longer term ionic stress and the early growth rate decline during salinity stress. We present, to our knowledge, a new approach to capture the dynamic plant responses to its environment and elucidate the genetic basis of these responses using a longitudinal genome-wide association model. PMID:26111541

Methodology Series Module 6: Systematic Reviews and Meta-analysis

PubMed Central

Setia, Maninder Singh

2016-01-01

Systematic reviews and meta-analysis have become an important of biomedical literature, and they provide the “highest level of evidence” for various clinical questions. There are a lot of studies – sometimes with contradictory conclusions – on a particular topic in literature. Hence, as a clinician, which results will you believe? What will you tell your patient? Which drug is better? A systematic review or a meta-analysis may help us answer these questions. In addition, it may also help us understand the quality of the articles in literature or the type of studies that have been conducted and published (example, randomized trials or observational studies). The first step it to identify a research question for systematic review or meta-analysis. The next step is to identify the articles that will be included in the study. This will be done by searching various databases; it is important that the researcher should search for articles in more than one database. It will also be useful to form a group of researchers and statisticians that have expertise in conducting systematic reviews and meta-analysis before initiating them. We strongly encourage the readers to register their proposed review/meta-analysis with PROSPERO. Finally, these studies should be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis checklist. PMID:27904176

Methodology Series Module 6: Systematic Reviews and Meta-analysis.

PubMed

Setia, Maninder Singh

2016-01-01

Systematic reviews and meta-analysis have become an important of biomedical literature, and they provide the "highest level of evidence" for various clinical questions. There are a lot of studies - sometimes with contradictory conclusions - on a particular topic in literature. Hence, as a clinician, which results will you believe? What will you tell your patient? Which drug is better? A systematic review or a meta-analysis may help us answer these questions. In addition, it may also help us understand the quality of the articles in literature or the type of studies that have been conducted and published (example, randomized trials or observational studies). The first step it to identify a research question for systematic review or meta-analysis. The next step is to identify the articles that will be included in the study. This will be done by searching various databases; it is important that the researcher should search for articles in more than one database. It will also be useful to form a group of researchers and statisticians that have expertise in conducting systematic reviews and meta-analysis before initiating them. We strongly encourage the readers to register their proposed review/meta-analysis with PROSPERO. Finally, these studies should be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis checklist.

From ecophysiology to phenomics: some implications of photoprotection and shade–sun acclimation in situ for dynamics of thylakoids in vitro

PubMed Central

Matsubara, Shizue; Förster, Britta; Waterman, Melinda; Robinson, Sharon A.; Pogson, Barry J.; Gunning, Brian; Osmond, Barry

2012-01-01

Half a century of research into the physiology and biochemistry of sun–shade acclimation in diverse plants has provided reality checks for contemporary understanding of thylakoid membrane dynamics. This paper reviews recent insights into photosynthetic efficiency and photoprotection from studies of two xanthophyll cycles in old shade leaves from the inner canopy of the tropical trees Inga sapindoides and Persea americana (avocado). It then presents new physiological data from avocado on the time frames of the slow coordinated photosynthetic development of sink leaves in sunlight and on the slow renovation of photosynthetic properties in old leaves during sun to shade and shade to sun acclimation. In so doing, it grapples with issues in vivo that seem relevant to our increasingly sophisticated understanding of ΔpH-dependent, xanthophyll-pigment-stabilized non-photochemical quenching in the antenna of PSII in thylakoid membranes in vitro. PMID:23148277

Omics studies of citrus, grape and rosaceae fruit trees

PubMed Central

Shiratake, Katsuhiro; Suzuki, Mami

2016-01-01

Recent advance of bioinformatics and analytical apparatuses such as next generation DNA sequencer (NGS) and mass spectrometer (MS) has brought a big wave of comprehensive study to biology. Comprehensive study targeting all genes, transcripts (RNAs), proteins, metabolites, hormones, ions or phenotypes is called genomics, transcriptomics, proteomics, metabolomics, hormonomics, ionomics or phenomics, respectively. These omics are powerful approaches to identify key genes for important traits, to clarify events of physiological mechanisms and to reveal unknown metabolic pathways in crops. Recently, the use of omics approach has increased dramatically in fruit tree research. Although the most reported omics studies on fruit trees are transcriptomics, proteomics and metabolomics, and a few is reported on hormonomics and ionomics. In this article, we reviewed recent omics studies of major fruit trees, i.e. citrus, grapevine and rosaceae fruit trees. The effectiveness and prospects of omics in fruit tree research will as well be highlighted. PMID:27069397

What can microbial genetics teach sociobiology?

PubMed Central

Foster, Kevin R.; Parkinson, Katie; Thompson, Christopher R.L.

2009-01-01

Progress in our understanding of sociobiology has occurred with little knowledge of the genetic mechanisms that underlie social traits. However, several recent studies have described microbial genes that affect social traits, thereby bringing genetics to sociobiology. A key finding is that simple genetic changes can have marked social consequences, and mutations that affect cheating and recognition behaviors have been discovered. The study of these mutants confirms a central theoretical prediction of social evolution: that genetic relatedness promotes cooperation. Microbial genetics also provides an important new perspective: that the genome-to-phenome mapping of social organisms might be organized to constrain the evolution of social cheaters. This constraint can occur both through pleiotropic genes that link cheating to a personal cost and through the existence of phoenix genes, which rescue cooperative systems from selfish and destructive strategies. These new insights show the power of studying microorganisms to improve our understanding of the evolution of cooperation. PMID:17207887

Fine-Tuning Tomato Agronomic Properties by Computational Genome Redesign

PubMed Central

Carrera, Javier; Fernández del Carmen, Asun; Fernández-Muñoz, Rafael; Rambla, Jose Luis; Pons, Clara; Jaramillo, Alfonso; Elena, Santiago F.; Granell, Antonio

2012-01-01

Considering cells as biofactories, we aimed to optimize its internal processes by using the same engineering principles that large industries are implementing nowadays: lean manufacturing. We have applied reverse engineering computational methods to transcriptomic, metabolomic and phenomic data obtained from a collection of tomato recombinant inbreed lines to formulate a kinetic and constraint-based model that efficiently describes the cellular metabolism from expression of a minimal core of genes. Based on predicted metabolic profiles, a close association with agronomic and organoleptic properties of the ripe fruit was revealed with high statistical confidence. Inspired in a synthetic biology approach, the model was used for exploring the landscape of all possible local transcriptional changes with the aim of engineering tomato fruits with fine-tuned biotechnological properties. The method was validated by the ability of the proposed genomes, engineered for modified desired agronomic traits, to recapitulate experimental correlations between associated metabolites. PMID:22685389

Genomics and functional genomics in Chlamydomonas reinhardtii

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blaby, Ian K.; Blaby-Haas, Crysten E.

The availability of the Chlamydomonas reinhardtii nuclear genome sequence continues to enable researchers to address biological questions relevant to algae, land plants and animals in unprecedented ways. As we continue to characterize and understand biological processes in C. reinhardtii and translate that knowledge to other systems, we are faced with the realization that many genes encode proteins without a defined function. The field of functional genomics aims to close this gap between genome sequence and protein function. Transcriptomes, proteomes and phenomes can each provide layers of gene-specific functional data while supplying a global snapshot of cellular behavior under different conditions.more » Herein we present a brief history of functional genomics, the present status of the C. reinhardtii genome, how genome-wide experiments can aid in supplying protein function inferences, and provide an outlook for functional genomics in C. reinhardtii.« less

Autonomous Unmanned Helicopter System for Remote Sensing Missions in Unknown Environments

NASA Astrophysics Data System (ADS)

Merz, T.; Chapman, S.

2011-09-01

This paper presents the design of an autonomous unmanned helicopter system for low-altitude remote sensing. The proposed concepts and methods are generic and not limited to a specific helicopter. The development was driven by the need for a dependable, modular, and affordable system with sufficient payload capacity suitable for both research and real-world deployment. The helicopter can be safely operated without a backup pilot in a contained area beyond visual range. This enables data collection in inaccessible or dangerous areas. Thanks to its terrain following and obstacle avoidance capability, the system does not require a priori information about terrain elevation and obstacles. Missions are specified in state diagrams and flight plans. We present performance characteristics of our system and show results of its deployment in real-world scenarios. We have successfully completed several dozen infrastructure inspection missions and crop monitoring missions facilitating plant phenomics studies.

Metabolomics in Sepsis and Its Impact on Public Health.

PubMed

Evangelatos, Nikolaos; Bauer, Pia; Reumann, Matthias; Satyamoorthy, Kapaettu; Lehrach, Hans; Brand, Angela

2017-01-01

Sepsis, with its often devastating consequences for patients and their families, remains a major public health concern that poses an increasing financial burden. Early resuscitation together with the elucidation of the biological pathways and pathophysiological mechanisms with the use of "-omics" technologies have started changing the clinical and research landscape in sepsis. Metabolomics (i.e., the study of the metabolome), an "-omics" technology further down in the "-omics" cascade between the genome and the phenome, could be particularly fruitful in sepsis research with the potential to alter the clinical practice. Apart from its benefit for the individual patient, metabolomics has an impact on public health that extends beyond its applications in medicine. In this review, we present recent developments in metabolomics research in sepsis, with a focus on pneumonia, and we discuss the impact of metabolomics on public health, with a focus on free/libre open source software. © 2018 S. Karger AG, Basel.

Genetics of the dentofacial variation in human malocclusion

PubMed Central

Moreno Uribe, L. M.; Miller, S. F.

2015-01-01

Malocclusions affect individuals worldwide, resulting in compromised function and esthetics. Understanding the etiological factors contributing to the variation in dentofacial morphology associated with malocclusions is the key to develop novel treatment approaches. Advances in dentofacial phenotyping, which is the comprehensive characterization of hard and soft tissue variation in the craniofacial complex, together with the acquisition of large-scale genomic data have started to unravel genetic mechanisms underlying facial variation. Knowledge on the genetics of human malocclusion is limited even though results attained thus far are encouraging, with promising opportunities for future research. This review summarizes the most common dentofacial variations associated with malocclusions and reviews the current knowledge of the roles of genes in the development of malocclusions. Lastly, this review will describe ways to advance malocclusion research, following examples from the expanding fields of phenomics and genomic medicine, which aim to better patient outcomes. PMID:25865537

A web accessible resource for investigating cassava phenomics and genomics information: BIOGEN BASE

PubMed Central

Jayakodi, Murukarthick; selvan, Sreedevi Ghokhilamani; Natesan, Senthil; Muthurajan, Raveendran; Duraisamy, Raghu; Ramineni, Jana Jeevan; Rathinasamy, Sakthi Ambothi; Karuppusamy, Nageswari; Lakshmanan, Pugalenthi; Chokkappan, Mohan

2011-01-01

The goal of our research is to establish a unique portal to bring out the potential outcome of the research in the Casssava crop. The Biogen base for cassava clearly brings out the variations of different traits of the germplasms, maintained at the Tapioca and Castor Research Station, Tamil Nadu Agricultural University. Phenotypic and genotypic variations of the accessions are clearly depicted, for the users to browse and interpret the variations using the microsatellite markers. Database (BIOGEN BASE ‐ CASSAVA) is designed using PHP and MySQL and is equipped with extensive search options. It is more user-friendly and made publicly available, to improve the research and development of cassava by making a wealth of genetics and genomics data available through open, common, and worldwide forum for all individuals interested in the field. Availability The database is available for free at http://www.tnaugenomics.com/biogenbase/casava.php PMID:21904428

A web accessible resource for investigating cassava phenomics and genomics information: BIOGEN BASE.

PubMed

Jayakodi, Murukarthick; Selvan, Sreedevi Ghokhilamani; Natesan, Senthil; Muthurajan, Raveendran; Duraisamy, Raghu; Ramineni, Jana Jeevan; Rathinasamy, Sakthi Ambothi; Karuppusamy, Nageswari; Lakshmanan, Pugalenthi; Chokkappan, Mohan

2011-01-01

The goal of our research is to establish a unique portal to bring out the potential outcome of the research in the Casssava crop. The Biogen base for cassava clearly brings out the variations of different traits of the germplasms, maintained at the Tapioca and Castor Research Station, Tamil Nadu Agricultural University. Phenotypic and genotypic variations of the accessions are clearly depicted, for the users to browse and interpret the variations using the microsatellite markers. Database (BIOGEN BASE - CASSAVA) is designed using PHP and MySQL and is equipped with extensive search options. It is more user-friendly and made publicly available, to improve the research and development of cassava by making a wealth of genetics and genomics data available through open, common, and worldwide forum for all individuals interested in the field. The database is available for free at http://www.tnaugenomics.com/biogenbase/casava.php.

Big Biomedical data as the key resource for discovery science

DOE Office of Scientific and Technical Information (OSTI.GOV)

Toga, Arthur W.; Foster, Ian; Kesselman, Carl

Modern biomedical data collection is generating exponentially more data in a multitude of formats. This flood of complex data poses significant opportunities to discover and understand the critical interplay among such diverse domains as genomics, proteomics, metabolomics, and phenomics, including imaging, biometrics, and clinical data. The Big Data for Discovery Science Center is taking an “-ome to home” approach to discover linkages between these disparate data sources by mining existing databases of proteomic and genomic data, brain images, and clinical assessments. In support of this work, the authors developed new technological capabilities that make it easy for researchers to manage,more » aggregate, manipulate, integrate, and model large amounts of distributed data. Guided by biological domain expertise, the Center’s computational resources and software will reveal relationships and patterns, aiding researchers in identifying biomarkers for the most confounding conditions and diseases, such as Parkinson’s and Alzheimer’s.« less

Big biomedical data as the key resource for discovery science

PubMed Central

Toga, Arthur W; Foster, Ian; Kesselman, Carl; Madduri, Ravi; Chard, Kyle; Deutsch, Eric W; Price, Nathan D; Glusman, Gustavo; Heavner, Benjamin D; Dinov, Ivo D; Ames, Joseph; Van Horn, John; Kramer, Roger; Hood, Leroy

2015-01-01

Modern biomedical data collection is generating exponentially more data in a multitude of formats. This flood of complex data poses significant opportunities to discover and understand the critical interplay among such diverse domains as genomics, proteomics, metabolomics, and phenomics, including imaging, biometrics, and clinical data. The Big Data for Discovery Science Center is taking an “-ome to home” approach to discover linkages between these disparate data sources by mining existing databases of proteomic and genomic data, brain images, and clinical assessments. In support of this work, the authors developed new technological capabilities that make it easy for researchers to manage, aggregate, manipulate, integrate, and model large amounts of distributed data. Guided by biological domain expertise, the Center’s computational resources and software will reveal relationships and patterns, aiding researchers in identifying biomarkers for the most confounding conditions and diseases, such as Parkinson’s and Alzheimer’s. PMID:26198305

Enabling Genomic-Phenomic Association Discovery without Sacrificing Anonymity

PubMed Central

Heatherly, Raymond D.; Loukides, Grigorios; Denny, Joshua C.; Haines, Jonathan L.; Roden, Dan M.; Malin, Bradley A.

2013-01-01

Health information technologies facilitate the collection of massive quantities of patient-level data. A growing body of research demonstrates that such information can support novel, large-scale biomedical investigations at a fraction of the cost of traditional prospective studies. While healthcare organizations are being encouraged to share these data in a de-identified form, there is hesitation over concerns that it will allow corresponding patients to be re-identified. Currently proposed technologies to anonymize clinical data may make unrealistic assumptions with respect to the capabilities of a recipient to ascertain a patients identity. We show that more pragmatic assumptions enable the design of anonymization algorithms that permit the dissemination of detailed clinical profiles with provable guarantees of protection. We demonstrate this strategy with a dataset of over one million medical records and show that 192 genotype-phenotype associations can be discovered with fidelity equivalent to non-anonymized clinical data. PMID:23405076

Genomics and functional genomics in Chlamydomonas reinhardtii

DOE PAGES

Blaby, Ian K.; Blaby-Haas, Crysten E.

2017-03-21

The availability of the Chlamydomonas reinhardtii nuclear genome sequence continues to enable researchers to address biological questions relevant to algae, land plants and animals in unprecedented ways. As we continue to characterize and understand biological processes in C. reinhardtii and translate that knowledge to other systems, we are faced with the realization that many genes encode proteins without a defined function. The field of functional genomics aims to close this gap between genome sequence and protein function. Transcriptomes, proteomes and phenomes can each provide layers of gene-specific functional data while supplying a global snapshot of cellular behavior under different conditions.more » Herein we present a brief history of functional genomics, the present status of the C. reinhardtii genome, how genome-wide experiments can aid in supplying protein function inferences, and provide an outlook for functional genomics in C. reinhardtii.« less

Omics studies of citrus, grape and rosaceae fruit trees.

PubMed

Shiratake, Katsuhiro; Suzuki, Mami

2016-01-01

Recent advance of bioinformatics and analytical apparatuses such as next generation DNA sequencer (NGS) and mass spectrometer (MS) has brought a big wave of comprehensive study to biology. Comprehensive study targeting all genes, transcripts (RNAs), proteins, metabolites, hormones, ions or phenotypes is called genomics, transcriptomics, proteomics, metabolomics, hormonomics, ionomics or phenomics, respectively. These omics are powerful approaches to identify key genes for important traits, to clarify events of physiological mechanisms and to reveal unknown metabolic pathways in crops. Recently, the use of omics approach has increased dramatically in fruit tree research. Although the most reported omics studies on fruit trees are transcriptomics, proteomics and metabolomics, and a few is reported on hormonomics and ionomics. In this article, we reviewed recent omics studies of major fruit trees, i.e. citrus, grapevine and rosaceae fruit trees. The effectiveness and prospects of omics in fruit tree research will as well be highlighted.

Technical Note: Introduction of variance component analysis to setup error analysis in radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsuo, Yukinori, E-mail: ymatsuo@kuhp.kyoto-u.ac.

Purpose: The purpose of this technical note is to introduce variance component analysis to the estimation of systematic and random components in setup error of radiotherapy. Methods: Balanced data according to the one-factor random effect model were assumed. Results: Analysis-of-variance (ANOVA)-based computation was applied to estimate the values and their confidence intervals (CIs) for systematic and random errors and the population mean of setup errors. The conventional method overestimates systematic error, especially in hypofractionated settings. The CI for systematic error becomes much wider than that for random error. The ANOVA-based estimation can be extended to a multifactor model considering multiplemore » causes of setup errors (e.g., interpatient, interfraction, and intrafraction). Conclusions: Variance component analysis may lead to novel applications to setup error analysis in radiotherapy.« less

A systematic review of systematic reviews of homeopathy

PubMed Central

Ernst, E

2002-01-01

Homeopathy remains one of the most controversial subjects in therapeutics. This article is an attempt to clarify its effectiveness based on recent systematic reviews. Electronic databases were searched for systematic reviews/meta-analysis on the subject. Seventeen articles fulfilled the inclusion/exclusion criteria. Six of them related to re-analyses of one landmark meta-analysis. Collectively they implied that the overall positive result of this meta-analysis is not supported by a critical analysis of the data. Eleven independent systematic reviews were located. Collectively they failed to provide strong evidence in favour of homeopathy. In particular, there was no condition which responds convincingly better to homeopathic treatment than to placebo or other control interventions. Similarly, there was no homeopathic remedy that was demonstrated to yield clinical effects that are convincingly different from placebo. It is concluded that the best clinical evidence for homeopathy available to date does not warrant positive recommendations for its use in clinical practice. PMID:12492603

How to Perform a Systematic Review and Meta-analysis of Diagnostic Imaging Studies.

PubMed

Cronin, Paul; Kelly, Aine Marie; Altaee, Duaa; Foerster, Bradley; Petrou, Myria; Dwamena, Ben A

2018-05-01

A systematic review is a comprehensive search, critical evaluation, and synthesis of all the relevant studies on a specific (clinical) topic that can be applied to the evaluation of diagnostic and screening imaging studies. It can be a qualitative or a quantitative (meta-analysis) review of available literature. A meta-analysis uses statistical methods to combine and summarize the results of several studies. In this review, a 12-step approach to performing a systematic review (and meta-analysis) is outlined under the four domains: (1) Problem Formulation and Data Acquisition, (2) Quality Appraisal of Eligible Studies, (3) Statistical Analysis of Quantitative Data, and (4) Clinical Interpretation of the Evidence. This review is specifically geared toward the performance of a systematic review and meta-analysis of diagnostic test accuracy (imaging) studies. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

UAV-Based Thermal Imaging for High-Throughput Field Phenotyping of Black Poplar Response to Drought

PubMed Central

Ludovisi, Riccardo; Tauro, Flavia; Salvati, Riccardo; Khoury, Sacha; Mugnozza Scarascia, Giuseppe; Harfouche, Antoine

2017-01-01

Poplars are fast-growing, high-yielding forest tree species, whose cultivation as second-generation biofuel crops is of increasing interest and can efficiently meet emission reduction goals. Yet, breeding elite poplar trees for drought resistance remains a major challenge. Worldwide breeding programs are largely focused on intra/interspecific hybridization, whereby Populus nigra L. is a fundamental parental pool. While high-throughput genotyping has resulted in unprecedented capabilities to rapidly decode complex genetic architecture of plant stress resistance, linking genomics to phenomics is hindered by technically challenging phenotyping. Relying on unmanned aerial vehicle (UAV)-based remote sensing and imaging techniques, high-throughput field phenotyping (HTFP) aims at enabling highly precise and efficient, non-destructive screening of genotype performance in large populations. To efficiently support forest-tree breeding programs, ground-truthing observations should be complemented with standardized HTFP. In this study, we develop a high-resolution (leaf level) HTFP approach to investigate the response to drought of a full-sib F2 partially inbred population (termed here ‘POP6’), whose F1 was obtained from an intraspecific P. nigra controlled cross between genotypes with highly divergent phenotypes. We assessed the effects of two water treatments (well-watered and moderate drought) on a population of 4603 trees (503 genotypes) hosted in two adjacent experimental plots (1.67 ha) by conducting low-elevation (25 m) flights with an aerial drone and capturing 7836 thermal infrared (TIR) images. TIR images were undistorted, georeferenced, and orthorectified to obtain radiometric mosaics. Canopy temperature (Tc) was extracted using two independent semi-automated segmentation techniques, eCognition- and Matlab-based, to avoid the mixed-pixel problem. Overall, results showed that the UAV platform-based thermal imaging enables to effectively assess genotype variability under drought stress conditions. Tc derived from aerial thermal imagery presented a good correlation with ground-truth stomatal conductance (gs) in both segmentation techniques. Interestingly, the HTFP approach was instrumental to detect drought-tolerant response in 25% of the population. This study shows the potential of UAV-based thermal imaging for field phenomics of poplar and other tree species. This is anticipated to have tremendous implications for accelerating forest tree genetic improvement against abiotic stress. PMID:29021803

Racial and ethnic differences in epilepsy classification among probands in the Epilepsy Phenome/Genome Project (EPGP).

PubMed

Friedman, Daniel; Fahlstrom, Robyn

2013-12-01

Little is known about the ethnic and racial differences in the prevalence of generalized and focal epilepsy among patients with non-acquired epilepsies. In this study, we examined epilepsy classification and race/ethnicity in 813 probands from sibling or parent-child pairs with epilepsy enrolled in the Epilepsy Genome/Phenome Project (EPGP). Subjects were classified as generalized epilepsy (GE), non-acquired focal epilepsy (NAFE), mixed epilepsy syndrome (both generalized and focal), and unclassifiable, based on consensus review of semiology and available clinical, electrophysiology, and neuroimaging data. In this cohort, 628 (77.2%) subjects identified exclusively as Caucasian/white and 65 (8.0%) subjects reported African ancestry, including subjects of mixed-race. Of the Caucasian/white subjects, 357 (56.8%) had GE, 207 (33.0%) had NAFE, 32 (5.1%) had a mixed syndrome, and 32 (5.1%) were unclassifiable. Among subjects of African ancestry, 28 (43.1%) had GE, 27 (41.5%) had NAFE, 2 (3.1%) had a mixed syndrome, and 8 (12.3%) were unclassifiable. There was a higher proportion of subjects with GE compared to other syndromes among Caucasians/whites compared to subjects with African ancestry (OR 1.74, 95% CI: 1.04-2.92, two-tailed Fisher's exact test, p=0.036). There was no difference in the rate of GE among subjects reporting Hispanic ethnicity (7.6% of total) when adjusted for race (Caucasian/white vs non-Caucasian/white; OR 0.65, 95% CI: 0.40-1.06, p>0.05). The proportion of participants with unclassifiable epilepsy was significantly greater in those of African-American descent. In a group of patients with epilepsy of unknown etiology and an affected first degree relative, GE is more common among Caucasian/white subjects than among those with African ancestry. These findings suggest there may be geographical differences in the distribution of epilepsy susceptibility genes and an effect of genetic background on epilepsy phenotype. However, the results should be interpreted with caution because of the low numbers of African-Americans in this cohort and more limited diagnostic data available for epilepsy classification in these subjects compared to Caucasians/whites. Copyright © 2013 Elsevier B.V. All rights reserved.

Evaluation of Borage Extracts As Potential Biostimulant Using a Phenomic, Agronomic, Physiological, and Biochemical Approach

PubMed Central

Bulgari, Roberta; Morgutti, Silvia; Cocetta, Giacomo; Negrini, Noemi; Farris, Stefano; Calcante, Aldo; Spinardi, Anna; Ferrari, Enrico; Mignani, Ilaria; Oberti, Roberto; Ferrante, Antonio

2017-01-01

Biostimulants are substances able to improve water and nutrient use efficiency and counteract stress factors by enhancing primary and secondary metabolism. Premise of the work was to exploit raw extracts from leaves (LE) or flowers (FE) of Borago officinalis L., to enhance yield and quality of Lactuca sativa ‘Longifolia,’ and to set up a protocol to assess their effects. To this aim, an integrated study on agronomic, physiological and biochemical aspects, including also a phenomic approach, has been adopted. Extracts were diluted to 1 or 10 mL L–1, sprayed onto lettuce plants at the middle of the growing cycle and 1 day before harvest. Control plants were treated with water. Non-destructive analyses were conducted to assess the effect of extracts on biomass with an innovative imaging technique, and on leaf photosynthetic efficiency (chlorophyll a fluorescence and leaf gas exchanges). At harvest, the levels of ethylene, photosynthetic pigments, nitrate, and primary (sucrose and total sugars) and secondary (total phenols and flavonoids) metabolites, including the activity and levels of phenylalanine ammonia lyase (PAL) were assessed. Moreover, a preliminary study of the effects during postharvest was performed. Borage extracts enhanced the primary metabolism by increasing leaf pigments and photosynthetic activity. Plant fresh weight increased upon treatments with 10 mL L–1 doses, as correctly estimated by multi-view angles images. Chlorophyll a fluorescence data showed that FEs were able to increase the number of active reaction centers per cross section; a similar trend was observed for the performance index. Ethylene was three-fold lower in FEs treatments. Nitrate and sugar levels did not change in response to the different treatments. Total flavonoids and phenols, as well as the total protein levels, the in vitro PAL specific activity, and the levels of PAL-like polypeptides were increased by all borage extracts, with particular regard to FEs. FEs also proved efficient in preventing degradation and inducing an increase in photosynthetic pigments during storage. In conclusion, borage extracts, with particular regard to the flower ones, appear to indeed exert biostimulant effects on lettuce; future work will be required to further investigate on their efficacy in different conditions and/or species. PMID:28638392

UAV-Based Thermal Imaging for High-Throughput Field Phenotyping of Black Poplar Response to Drought.

PubMed

Ludovisi, Riccardo; Tauro, Flavia; Salvati, Riccardo; Khoury, Sacha; Mugnozza Scarascia, Giuseppe; Harfouche, Antoine

2017-01-01

Poplars are fast-growing, high-yielding forest tree species, whose cultivation as second-generation biofuel crops is of increasing interest and can efficiently meet emission reduction goals. Yet, breeding elite poplar trees for drought resistance remains a major challenge. Worldwide breeding programs are largely focused on intra/interspecific hybridization, whereby Populus nigra L. is a fundamental parental pool. While high-throughput genotyping has resulted in unprecedented capabilities to rapidly decode complex genetic architecture of plant stress resistance, linking genomics to phenomics is hindered by technically challenging phenotyping. Relying on unmanned aerial vehicle (UAV)-based remote sensing and imaging techniques, high-throughput field phenotyping (HTFP) aims at enabling highly precise and efficient, non-destructive screening of genotype performance in large populations. To efficiently support forest-tree breeding programs, ground-truthing observations should be complemented with standardized HTFP. In this study, we develop a high-resolution (leaf level) HTFP approach to investigate the response to drought of a full-sib F 2 partially inbred population (termed here 'POP6'), whose F 1 was obtained from an intraspecific P. nigra controlled cross between genotypes with highly divergent phenotypes. We assessed the effects of two water treatments (well-watered and moderate drought) on a population of 4603 trees (503 genotypes) hosted in two adjacent experimental plots (1.67 ha) by conducting low-elevation (25 m) flights with an aerial drone and capturing 7836 thermal infrared (TIR) images. TIR images were undistorted, georeferenced, and orthorectified to obtain radiometric mosaics. Canopy temperature ( T c ) was extracted using two independent semi-automated segmentation techniques, eCognition- and Matlab-based, to avoid the mixed-pixel problem. Overall, results showed that the UAV platform-based thermal imaging enables to effectively assess genotype variability under drought stress conditions. T c derived from aerial thermal imagery presented a good correlation with ground-truth stomatal conductance ( g s ) in both segmentation techniques. Interestingly, the HTFP approach was instrumental to detect drought-tolerant response in 25% of the population. This study shows the potential of UAV-based thermal imaging for field phenomics of poplar and other tree species. This is anticipated to have tremendous implications for accelerating forest tree genetic improvement against abiotic stress.

Sinking towards destiny: High throughput measurement of phytoplankton sinking rates through time-resolved fluorescence plate spectroscopy.

PubMed

Bannon, Catherine C; Campbell, Douglas A

2017-01-01

Diatoms are marine primary producers that sink in part due to the density of their silica frustules. Sinking of these phytoplankters is crucial for both the biological pump that sequesters carbon to the deep ocean and for the life strategy of the organism. Sinking rates have been previously measured through settling columns, or with fluorimeters or video microscopy arranged perpendicularly to the direction of sinking. These side-view techniques require large volumes of culture, specialized equipment and are difficult to scale up to multiple simultaneous measures for screening. We established a method for parallel, large scale analysis of multiple phytoplankton sinking rates through top-view monitoring of chlorophyll a fluorescence in microtitre well plates. We verified the method through experimental analysis of known factors that influence sinking rates, including exponential versus stationary growth phase in species of different cell sizes; Thalassiosira pseudonana CCMP1335, chain-forming Skeletonema marinoi RO5A and Coscinodiscus radiatus CCMP312. We fit decay curves to an algebraic transform of the decrease in fluorescence signal as cells sank away from the fluorometer detector, and then used minimal mechanistic assumptions to extract a sinking rate (m d-1) using an RStudio script, SinkWORX. We thereby detected significant differences in sinking rates as larger diatom cells sank faster than smaller cells, and cultures in stationary phase sank faster than those in exponential phase. Our sinking rate estimates accord well with literature values from previously established methods. This well plate-based method can operate as a high throughput integrative phenotypic screen for factors that influence sinking rates including macromolecular allocations, nutrient availability or uptake rates, chain-length or cell size, degree of silification and progression through growth stages. Alternately the approach can be used to phenomically screen libraries of mutants.

Association between borderline dysnatremia and mortality insight into a new data mining approach.

PubMed

Girardeau, Yannick; Jannot, Anne-Sophie; Chatellier, Gilles; Saint-Jean, Olivier

2017-11-22

Even small variations of serum sodium concentration may be associated with mortality. Our objective was to confirm the impact of borderline dysnatremia for patients admitted to hospital on in-hospital mortality using real life care data from our electronic health record (EHR) and a phenome-wide association analysis (PheWAS). Retrospective observational study based on patient data admitted to Hôpital Européen George Pompidou, between 01/01/2008 and 31/06/2014; including 45,834 patients with serum sodium determinations on admission. We analyzed the association between dysnatremia and in-hospital mortality, using a multivariate logistic regression model to adjust for classical potential confounders. We performed a PheWAS to identify new potential confounders. Hyponatremia and hypernatremia were recorded for 12.0% and 1.0% of hospital stays, respectively. Adjusted odds ratios (ORa) for severe, moderate and borderline hyponatremia were 3.44 (95% CI, 2.41-4.86), 2.48 (95% CI, 1.96-3.13) and 1.98 (95% CI, 1.73-2.28), respectively. ORa for severe, moderate and borderline hypernatremia were 4.07 (95% CI, 2.92-5.62), 4.42 (95% CI, 2.04-9.20) and 3.72 (95% CI, 1.53-8.45), respectively. Borderline hyponatremia (ORa = 1.57 95% CI, 1.35-1.81) and borderline hypernatremia (ORa = 3.47 95% CI, 2.43-4.90) were still associated with in-hospital mortality after adjustment for classical and new confounding factors identified through the PheWAS analysis. Borderline dysnatremia on admission are independently associated with a higher risk of in-hospital mortality. By using medical data automatically collected in EHR and a new data mining approach, we identified new potential confounding factors that were highly associated with both mortality and dysnatremia.

Catalog of MicroRNA Seed Polymorphisms in Vertebrates

PubMed Central

Calin, George Adrian; Horvat, Simon; Jiang, Zhihua; Dovc, Peter; Kunej, Tanja

2012-01-01

MicroRNAs (miRNAs) are a class of non-coding RNA that plays an important role in posttranscriptional regulation of mRNA. Evidence has shown that miRNA gene variability might interfere with its function resulting in phenotypic variation and disease susceptibility. A major role in miRNA target recognition is ascribed to complementarity with the miRNA seed region that can be affected by polymorphisms. In the present study, we developed an online tool for the detection of miRNA polymorphisms (miRNA SNiPer) in vertebrates (http://www.integratomics-time.com/miRNA-SNiPer) and generated a catalog of miRNA seed region polymorphisms (miR-seed-SNPs) consisting of 149 SNPs in six species. Although a majority of detected polymorphisms were due to point mutations, two consecutive nucleotide substitutions (double nucleotide polymorphisms, DNPs) were also identified in nine miRNAs. We determined that miR-SNPs are frequently located within the quantitative trait loci (QTL), chromosome fragile sites, and cancer susceptibility loci, indicating their potential role in the genetic control of various complex traits. To test this further, we performed an association analysis between the mmu-miR-717 seed SNP rs30372501, which is polymorphic in a large number of standard inbred strains, and all phenotypic traits in these strains deposited in the Mouse Phenome Database. Analysis showed a significant association between the mmu-miR-717 seed SNP and a diverse array of traits including behavior, blood-clinical chemistry, body weight size and growth, and immune system suggesting that seed SNPs can indeed have major pleiotropic effects. The bioinformatics analyses, data and tools developed in the present study can serve researchers as a starting point in testing more targeted hypotheses and designing experiments using optimal species or strains for further mechanistic studies. PMID:22303453

Falls Prevention Education for Older Adults during and after Hospitalization: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Lee, Den-Ching A.; Pritchard, Elizabeth; McDermott, Fiona; Haines, Terry P.

2014-01-01

Objectives: To assess the effectiveness of patient education in reducing falls, promoting behavioural change and the uptake of prevention activities in older adults during and after hospitalization. Design: Systematic review and meta-analysis. Methods: A systematic search of five health science databases was performed up to November 2012. Studies…

[Report quality evaluation of systematic review or Meta-analysis published in China Journal of Chinese Materia Medica].

PubMed

Zhang, Yan; Yu, Dan-Dan; Cui, De-Hua; Liao, Xing; Guo, Hua

2018-03-01

To evaluate the report quality of intervention-related systematic reviews or Meta-analysis published in China Journal of Chinese Materia Medica, we searched CNKI and China Journal of Chinese Materia Medica webpages to collect intervention-related systematic reviews or Meta-analysis since the first issue of the magazine. A total of 40 systematic reviews or Meta-analysis reports were included, including one network Meta-analysis. According to the PRISMA statement published in 2009, the report quality of the systematic reviews or Meta-analysis was evaluated. According to the results, 3 had the low quality, 30 had the medium quality, and 7 had the high quality. The average score for all of items was 30 points (21-30.5 points for the medium quality). The 17 high-quality (31-40 points) report items were title, rationale, objectives, information sources, study selection, data collection process, data items, risk of bias in individual studies, summary measures, risk of bias across studies, study selection, study characteristics, risk of bias within studies, results of individual studies, synthesis of results, risk of bias across studies and funding; the 4 medium-quality (21-30.5 points) reporting items were eligibility criteria, search, limitations and conclusions; and the 6 low-quality (<=20.5 points) reporting items were structured summary, protocol and registration, synthesis of results, additional analysis (No.16), additional analysis (No.23) and summary of evidence. Through the analysis, it is found that the report quality of intervention-related systematic reviews or Meta-analysis published in China Journal of Chinese Materia Medica is medium, and it is necessary to improve the quality standard of the report. Copyright© by the Chinese Pharmaceutical Association.

Cluster analysis and subgrouping to investigate inter-individual variability to non-invasive brain stimulation: a systematic review.

PubMed

Pellegrini, Michael; Zoghi, Maryam; Jaberzadeh, Shapour

2018-01-12

Cluster analysis and other subgrouping techniques have risen in popularity in recent years in non-invasive brain stimulation research in the attempt to investigate the issue of inter-individual variability - the issue of why some individuals respond, as traditionally expected, to non-invasive brain stimulation protocols and others do not. Cluster analysis and subgrouping techniques have been used to categorise individuals, based on their response patterns, as responder or non-responders. There is, however, a lack of consensus and consistency on the most appropriate technique to use. This systematic review aimed to provide a systematic summary of the cluster analysis and subgrouping techniques used to date and suggest recommendations moving forward. Twenty studies were included that utilised subgrouping techniques, while seven of these additionally utilised cluster analysis techniques. The results of this systematic review appear to indicate that statistical cluster analysis techniques are effective in identifying subgroups of individuals based on response patterns to non-invasive brain stimulation. This systematic review also reports a lack of consensus amongst researchers on the most effective subgrouping technique and the criteria used to determine whether an individual is categorised as a responder or a non-responder. This systematic review provides a step-by-step guide to carrying out statistical cluster analyses and subgrouping techniques to provide a framework for analysis when developing further insights into the contributing factors of inter-individual variability in response to non-invasive brain stimulation.

A Pilot Systematic Review and Meta-Analysis on the Effectiveness of Problem Based Learning.

ERIC Educational Resources Information Center

Newman, Mark

This paper reports on the development and piloting of a systematic review and meta analysis of research on the effectiveness of problem based learning (PBL). The systematic review protocol was pilot tested with a sample of studies cited as providing "evidence" about the effectiveness of PBL. From the 5 studies mentioned in the sample of reviews,…

Additional considerations are required when preparing a protocol for a systematic review with multiple interventions.

PubMed

Chaimani, Anna; Caldwell, Deborah M; Li, Tianjing; Higgins, Julian P T; Salanti, Georgia

2017-03-01

The number of systematic reviews that aim to compare multiple interventions using network meta-analysis is increasing. In this study, we highlight aspects of a standard systematic review protocol that may need modification when multiple interventions are to be compared. We take the protocol format suggested by Cochrane for a standard systematic review as our reference and compare the considerations for a pairwise review with those required for a valid comparison of multiple interventions. We suggest new sections for protocols of systematic reviews including network meta-analyses with a focus on how to evaluate their assumptions. We provide example text from published protocols to exemplify the considerations. Standard systematic review protocols for pairwise meta-analyses need extensions to accommodate the increased complexity of network meta-analysis. Our suggested modifications are widely applicable to both Cochrane and non-Cochrane systematic reviews involving network meta-analyses. Copyright © 2017 Elsevier Inc. All rights reserved.

Post-genomic behavioral genetics: From revolution to routine.

PubMed

Ashbrook, D G; Mulligan, M K; Williams, R W

2018-03-01

What was once expensive and revolutionary-full-genome sequence-is now affordable and routine. Costs will continue to drop, opening up new frontiers in behavioral genetics. This shift in costs from the genome to the phenome is most notable in large clinical studies of behavior and associated diseases in cohorts that exceed hundreds of thousands of subjects. Examples include the Women's Health Initiative (www.whi.org), the Million Veterans Program (www. va.gov/MVP), the 100 000 Genomes Project (genomicsengland.co.uk) and commercial efforts such as those by deCode (www.decode.com) and 23andme (www.23andme.com). The same transition is happening in experimental neuro- and behavioral genetics, and sample sizes of many hundreds of cases are becoming routine (www.genenetwork.org, www.mousephenotyping.org). There are two major consequences of this new affordability of massive omics datasets: (1) it is now far more practical to explore genetic modulation of behavioral differences and the key role of gene-by-environment interactions. Researchers are already doing the hard part-the quantitative analysis of behavior. Adding the omics component can provide powerful links to molecules, cells, circuits and even better treatment. (2) There is an acute need to highlight and train behavioral scientists in how best to exploit new omics approaches. This review addresses this second issue and highlights several new trends and opportunities that will be of interest to experts in animal and human behaviors. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Genetic and Computational Approaches for Studying Plant Development and Abiotic Stress Responses Using Image-Based Phenotyping

NASA Astrophysics Data System (ADS)

Campbell, M. T.; Walia, H.; Grondin, A.; Knecht, A.

2017-12-01

The development of abiotic stress tolerant crops (i.e. drought, salinity, or heat stress) requires the discovery of DNA sequence variants associated with stress tolerance-related traits. However, many traits underlying adaptation to abiotic stress involve a suite of physiological pathways that may be induced at different times throughout the duration of stress. Conventional single-point phenotyping approaches fail to fully capture these temporal responses, and thus downstream genetic analysis may only identify a subset of the genetic variants that are important for adaptation to sub-optimal environments. Although genomic resources for crops have advanced tremendously, the collection of phenotypic data for morphological and physiological traits is laborious and remains a significant bottleneck in bridging the phenotype-genotype gap. In recent years, the availability of automated, image-based phenotyping platforms has provided researchers with an opportunity to collect morphological and physiological traits non-destructively in a highly controlled environment. Moreover, these platforms allow abiotic stress responses to be recorded throughout the duration of the experiment, and have facilitated the use of function-valued traits for genetic analyses in major crops. We will present our approaches for addressing abiotic stress tolerance in cereals. This talk will focus on novel open-source software to process and extract biological meaningful data from images generated from these phenomics platforms. In addition, we will discuss the statistical approaches to model longitudinal phenotypes and dissect the genetic basis of dynamic responses to these abiotic stresses throughout development.

The human-induced pluripotent stem cell initiative-data resources for cellular genetics.

PubMed

Streeter, Ian; Harrison, Peter W; Faulconbridge, Adam; Flicek, Paul; Parkinson, Helen; Clarke, Laura

2017-01-04

The Human Induced Pluripotent Stem Cell Initiative (HipSci) isf establishing a large catalogue of human iPSC lines, arguably the most well characterized collection to date. The HipSci portal enables researchers to choose the right cell line for their experiment, and makes HipSci's rich catalogue of assay data easy to discover and reuse. Each cell line has genomic, transcriptomic, proteomic and cellular phenotyping data. Data are deposited in the appropriate EMBL-EBI archives, including the European Nucleotide Archive (ENA), European Genome-phenome Archive (EGA), ArrayExpress and PRoteomics IDEntifications (PRIDE) databases. The project will make 500 cell lines from healthy individuals, and from 150 patients with rare genetic diseases; these will be available through the European Collection of Authenticated Cell Cultures (ECACC). As of August 2016, 238 cell lines are available for purchase. Project data is presented through the HipSci data portal (http://www.hipsci.org/lines) and is downloadable from the associated FTP site (ftp://ftp.hipsci.ebi.ac.uk/vol1/ftp). The data portal presents a summary matrix of the HipSci cell lines, showing available data types. Each line has its own page containing descriptive metadata, quality information, and links to archived assay data. Analysis results are also available in a Track Hub, allowing visualization in the context of public genomic annotations (http://www.hipsci.org/data/trackhubs). © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Genetics and phenomics of inherited and sporadic non-autoimmune hyperthyroidism.

PubMed

Gozu, Hulya Iliksu; Lublinghoff, Julia; Bircan, Rifat; Paschke, Ralf

2010-06-30

TSH receptor (TSHR) germline mutations occur as activating mutations in familial non-autoimmune hyperthyroidism (FNAH) or sporadic non-autoimmune hyperthyroidism (SNAH). Up to date 17 constitutively activating TSHR mutations have been reported in 24 families with FNAH. The diagnosis of FNAH should be considered in cases with a positive family history, early onset of hyperthyroidism, goiter, absence of clinical stigmata of autoimmunity and recurrent hyperthyroidism. Moreover, 14 subjects with sporadic non-autoimmune hyperthyroidism and 10 different TSH receptor germline mutations have been reported. The main characteristic of SNAH is a negative family history. Additional consequences of prolonged neonatal hyperthyroidism (mental retardation, speech disturbances and craniosynostosis) have often been reported in SNAH. No genotype-phenotype relationship has been reported in patients with germline TSHR mutations. There is no association of in vitro activities determined by linear regression analysis (LRA) and several clinical indicators of hyperthyroidism activity for SNAH. However, the comparison of the LRA values of sporadic TSHR mutations with LRA values of familial TSHR mutations does show a significantly higher median LRA value for sporadic as compared to familial autosomal dominant hyperthyroidism. This finding is in line with the clinical impression of a more active clinical course in patients with SNAH. However, additional genetic, constitutional or environmental factors are most likely responsible for the phenotypic variations of the disease and the lack of correlation between in vitro activities of the TSHR mutations and the severity of hyperthyroidism. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Quantitative Trait Loci for Yield and Yield-Related Traits in Spring Barley Populations Derived from Crosses between European and Syrian Cultivars

PubMed Central

Krystkowiak, Karolina; Sawikowska, Aneta; Frohmberg, Wojciech; Górny, Andrzej; Kędziora, Andrzej; Jankowiak, Janusz; Józefczyk, Damian; Karg, Grzegorz; Andrusiak, Joanna; Krajewski, Paweł; Szarejko, Iwona; Surma, Maria; Adamski, Tadeusz; Guzy-Wróbelska, Justyna; Kuczyńska, Anetta

2016-01-01

In response to climatic changes, breeding programmes should be aimed at creating new cultivars with improved resistance to water scarcity. The objective of this study was to examine the yield potential of barley recombinant inbred lines (RILs) derived from three cross-combinations of European and Syrian spring cultivars, and to identify quantitative trait loci (QTLs) for yield-related traits in these populations. RILs were evaluated in field experiments over a period of three years (2011 to 2013) and genotyped with simple sequence repeat (SSR) and single nucleotide polymorphism (SNP) markers; a genetic map for each population was constructed and then one consensus map was developed. Biological interpretation of identified QTLs was achieved by reference to Ensembl Plants barley gene space. Twelve regions in the genomes of studied RILs were distinguished after QTL analysis. Most of the QTLs were identified on the 2H chromosome, which was the hotspot region in all three populations. Syrian parental cultivars contributed alleles decreasing traits' values at majority of QTLs for grain weight, grain number, spike length and time to heading, and numerous alleles increasing stem length. The phenomic and molecular approaches distinguished the lines with an acceptable grain yield potential combining desirable features or alleles from their parents, that is, early heading from the Syrian breeding line (Cam/B1/CI08887//CI05761) and short plant stature from the European semidwarf cultivar (Maresi). PMID:27227880

State-Space Formulation for Circuit Analysis

ERIC Educational Resources Information Center

Martinez-Marin, T.

2010-01-01

This paper presents a new state-space approach for temporal analysis of electrical circuits. The method systematically obtains the state-space formulation of nondegenerate linear networks without using concepts of topology. It employs nodal/mesh systematic analysis to reduce the number of undesired variables. This approach helps students to…

Complex systematic review - Perioperative antibiotics in conjunction with dental implant placement.

PubMed

Lund, Bodil; Hultin, Margareta; Tranaeus, Sofia; Naimi-Akbar, Aron; Klinge, Björn

2015-09-01

The aim of this study was to revisit the available scientific literature regarding perioperative antibiotics in conjunction with implant placement by combining the recommended methods for systematic reviews and complex systematic reviews. A search of Medline (OVID), The Cochrane Library (Wiley), EMBASE, PubMed and Health technology assessment (HTA) organizations was performed, in addition to a complementary hand-search. Selected systematic reviews and primary studies were assessed using GRADE and AMSTAR, respectively. A meta-analysis was performed. The literature search identified 846 papers of which 10 primary studies and seven systematic reviews were included. Quality assessment of the systematic reviews revealed two studies of moderate risk of bias and five with high risk of bias. The two systematic reviews of moderate risk of bias stated divergent numbers needed to treat (NNT) to prevent one patient from implant failure. Four of the primary studies comparing antibiotic prophylaxis with placebo were estimated to be of low, or moderate, risk of bias and subjected to meta-analysis. The NNT was 50 (pooled RR 0.39, 95% CI 0.18, 0.84; P = 0.02). None of these four studies individually show a statistical significant benefit of antibiotic prophylaxis. Furthermore, narrative analysis of the studies eligible for meta-analysis reveals clinical heterogeneity regarding intervention and smoking. Antibiotic prophylaxis in conjunction with implant placement reduced the risk for implant loss by 2%. However, the sub-analysis of the primary studies suggests that there is no benefit of antibiotic prophylaxis in uncomplicated implant surgery in healthy patient. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Targeted agents for patients with advanced/metastatic pancreatic cancer: A protocol for systematic review and network meta-analysis.

PubMed

Di, Baoshan; Pan, Bei; Ge, Long; Ma, Jichun; Wu, Yiting; Guo, Tiankang

2018-03-01

Pancreatic cancer (PC) is a devastating malignant tumor. Although surgical resection may offer a good prognosis and prolong survival, approximately 80% patients with PC are always diagnosed as unresectable tumor. National Comprehensive Cancer Network's (NCCN) recommended gemcitabine-based chemotherapy as efficient treatment. While, according to recent studies, targeted agents might be a better available option for advanced or metastatic pancreatic cancer patients. The aim of this systematic review and network meta-analysis will be to examine the differences of different targeted interventions for advanced/metastatic PC patients. We will conduct this systematic review and network meta-analysis using Bayesian method and according to Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) statement. To identify relevant studies, 6 electronic databases including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of science, CNKI (Chinese National Knowledge Infrastructure), and CBM (Chinese Biological Medical Database) will be searched. The risk of bias in included randomized controlled trials (RCTs) will be assessed using the Cochrane Handbook version 5.1.0. And we will use GRADE approach to assess the quality of evidence from network meta-analysis. Data will be analyzed using R 3.4.1 software. To the best of our knowledge, this systematic review and network meta-analysis will firstly use both direct and indirect evidence to compare the differences of different targeted agents and targeted agents plus chemotherapy for advanced/metastatic pancreatic cancer patients. This is a protocol of systematic review and meta-analysis, so the ethical approval and patient consent are not required. We will disseminate the results of this review by submitting to a peer-reviewed journal.

ABERRANT RESTING-STATE BRAIN ACTIVITY IN POSTTRAUMATIC STRESS DISORDER: A META-ANALYSIS AND SYSTEMATIC REVIEW.

PubMed

Koch, Saskia B J; van Zuiden, Mirjam; Nawijn, Laura; Frijling, Jessie L; Veltman, Dick J; Olff, Miranda

2016-07-01

About 10% of trauma-exposed individuals develop PTSD. Although a growing number of studies have investigated resting-state abnormalities in PTSD, inconsistent results suggest a need for a meta-analysis and a systematic review. We conducted a systematic literature search in four online databases using keywords for PTSD, functional neuroimaging, and resting-state. In total, 23 studies matched our eligibility criteria. For the meta-analysis, we included 14 whole-brain resting-state studies, reporting data on 663 participants (298 PTSD patients and 365 controls). We used the activation likelihood estimation approach to identify concurrence of whole-brain hypo- and hyperactivations in PTSD patients during rest. Seed-based studies could not be included in the quantitative meta-analysis. Therefore, a separate qualitative systematic review was conducted on nine seed-based functional connectivity studies. The meta-analysis showed consistent hyperactivity in the ventral anterior cingulate cortex and the parahippocampus/amygdala, but hypoactivity in the (posterior) insula, cerebellar pyramis and middle frontal gyrus in PTSD patients, compared to healthy controls. Partly concordant with these findings, the systematic review on seed-based functional connectivity studies showed enhanced salience network (SN) connectivity, but decreased default mode network (DMN) connectivity in PTSD. Combined, these altered resting-state connectivity and activity patterns could represent neurobiological correlates of increased salience processing and hypervigilance (SN), at the cost of awareness of internal thoughts and autobiographical memory (DMN) in PTSD. However, several discrepancies between findings of the meta-analysis and systematic review were observed, stressing the need for future studies on resting-state abnormalities in PTSD patients. © 2016 Wiley Periodicals, Inc.

Scientific publications on systematic review and meta-analysis from Chinese authors: a 10-year survey of the English literature.

PubMed

Yang, Zhiping; Wu, Qiong; Wu, Kaichun; Fan, Daiming

2012-03-01

Systematic reviews and meta-analyses are playing an increasingly important role in clinical research and practice. This study aimed to measure the scientific production of systematic review and meta-analysis from the three major regions of China: the Mainland (ML), Hong Kong (HK), and Taiwan (TW). English articles on systematic review and meta-analysis from ML, HK, and TW from 2001 to 2010 were retrieved from the PubMed database. The total number of articles, impact factors (IF), and articles published in high-impact journals were conducted for quantity and quality comparisons among the three regions. There were 1 587 published articles from ML (1 292), HK (203), and TW (92) during the past ten years. The annual total numbers of articles in the three regions increased significantly from 2001 to 2010 (from 13 to 677). The number of articles from ML has exceeded that from TW since 2001, and surpassed that from HK in 2003. The accumulated IF of articles from ML (3 488.24) was higher than those from HK (493.16) and TW (216.39). HK had the highest average IF of 3.31, followed by ML of 2.90 and TW of 2.85. Researchers from HK published a larger proportion of papers in high-impact journals than those from ML and TW. The Cochrane Database of Systematic Reviews was the most popular journal in China. Chinese authors have been very active to enhance the systematic review and meta-analysis research over the past ten years, especially in ML. The gap between ML and the other two regions has been narrowed. But there is still considerable room for Chinese authors to improve their studies on systematic review and meta-analysis.

Disease Model Discovery from 3,328 Gene Knockouts by The International Mouse Phenotyping Consortium

PubMed Central

Meehan, Terrence F.; Conte, Nathalie; West, David B.; Jacobsen, Julius O.; Mason, Jeremy; Warren, Jonathan; Chen, Chao-Kung; Tudose, Ilinca; Relac, Mike; Matthews, Peter; Karp, Natasha; Santos, Luis; Fiegel, Tanja; Ring, Natalie; Westerberg, Henrik; Greenaway, Simon; Sneddon, Duncan; Morgan, Hugh; Codner, Gemma F; Stewart, Michelle E; Brown, James; Horner, Neil; Haendel, Melissa; Washington, Nicole; Mungall, Christopher J.; Reynolds, Corey L; Gallegos, Juan; Gailus-Durner, Valerie; Sorg, Tania; Pavlovic, Guillaume; Bower, Lynette R; Moore, Mark; Morse, Iva; Gao, Xiang; Tocchini-Valentini, Glauco P; Obata, Yuichi; Cho, Soo Young; Seong, Je Kyung; Seavitt, John; Beaudet, Arthur L.; Dickinson, Mary E.; Herault, Yann; Wurst, Wolfgang; de Angelis, Martin Hrabe; Lloyd, K.C. Kent; Flenniken, Ann M; Nutter, Lauryl MJ; Newbigging, Susan; McKerlie, Colin; Justice, Monica J.; Murray, Stephen A.; Svenson, Karen L.; Braun, Robert E.; White, Jacqueline K.; Bradley, Allan; Flicek, Paul; Wells, Sara; Skarnes, William C.; Adams, David J.; Parkinson, Helen; Mallon, Ann-Marie; Brown, Steve D.M.; Smedley, Damian

2017-01-01

Although next generation sequencing has revolutionised the ability to associate variants with human diseases, diagnostic rates and development of new therapies are still limited by our lack of knowledge of function and pathobiological mechanism for most genes. To address this challenge, the International Mouse Phenotyping Consortium (IMPC) is creating a genome- and phenome-wide catalogue of gene function by characterizing new knockout mouse strains across diverse biological systems through a broad set of standardised phenotyping tests, with all mice made readily available to the biomedical community. Analysing the first 3328 genes reveals models for 360 diseases including the first for type C Bernard-Soulier, Bardet-Biedl-5 and Gordon Holmes syndromes. 90% of our phenotype annotations are novel, providing the first functional evidence for 1092 genes and candidates in unsolved diseases such as Arrhythmogenic Right Ventricular Dysplasia 3. Finally, we describe our role in variant functional validation with the 100,000 Genomes and other projects. PMID:28650483

Big biomedical data as the key resource for discovery science.

PubMed

Toga, Arthur W; Foster, Ian; Kesselman, Carl; Madduri, Ravi; Chard, Kyle; Deutsch, Eric W; Price, Nathan D; Glusman, Gustavo; Heavner, Benjamin D; Dinov, Ivo D; Ames, Joseph; Van Horn, John; Kramer, Roger; Hood, Leroy

2015-11-01

Modern biomedical data collection is generating exponentially more data in a multitude of formats. This flood of complex data poses significant opportunities to discover and understand the critical interplay among such diverse domains as genomics, proteomics, metabolomics, and phenomics, including imaging, biometrics, and clinical data. The Big Data for Discovery Science Center is taking an "-ome to home" approach to discover linkages between these disparate data sources by mining existing databases of proteomic and genomic data, brain images, and clinical assessments. In support of this work, the authors developed new technological capabilities that make it easy for researchers to manage, aggregate, manipulate, integrate, and model large amounts of distributed data. Guided by biological domain expertise, the Center's computational resources and software will reveal relationships and patterns, aiding researchers in identifying biomarkers for the most confounding conditions and diseases, such as Parkinson's and Alzheimer's. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Are there laws of genome evolution?

PubMed

Koonin, Eugene V

2011-08-01

Research in quantitative evolutionary genomics and systems biology led to the discovery of several universal regularities connecting genomic and molecular phenomic variables. These universals include the log-normal distribution of the evolutionary rates of orthologous genes; the power law-like distributions of paralogous family size and node degree in various biological networks; the negative correlation between a gene's sequence evolution rate and expression level; and differential scaling of functional classes of genes with genome size. The universals of genome evolution can be accounted for by simple mathematical models similar to those used in statistical physics, such as the birth-death-innovation model. These models do not explicitly incorporate selection; therefore, the observed universal regularities do not appear to be shaped by selection but rather are emergent properties of gene ensembles. Although a complete physical theory of evolutionary biology is inconceivable, the universals of genome evolution might qualify as "laws of evolutionary genomics" in the same sense "law" is understood in modern physics.

High-Throughput Phenotyping and QTL Mapping Reveals the Genetic Architecture of Maize Plant Growth.

PubMed

Zhang, Xuehai; Huang, Chenglong; Wu, Di; Qiao, Feng; Li, Wenqiang; Duan, Lingfeng; Wang, Ke; Xiao, Yingjie; Chen, Guoxing; Liu, Qian; Xiong, Lizhong; Yang, Wanneng; Yan, Jianbing

2017-03-01

With increasing demand for novel traits in crop breeding, the plant research community faces the challenge of quantitatively analyzing the structure and function of large numbers of plants. A clear goal of high-throughput phenotyping is to bridge the gap between genomics and phenomics. In this study, we quantified 106 traits from a maize ( Zea mays ) recombinant inbred line population ( n = 167) across 16 developmental stages using the automatic phenotyping platform. Quantitative trait locus (QTL) mapping with a high-density genetic linkage map, including 2,496 recombinant bins, was used to uncover the genetic basis of these complex agronomic traits, and 988 QTLs have been identified for all investigated traits, including three QTL hotspots. Biomass accumulation and final yield were predicted using a combination of dissected traits in the early growth stage. These results reveal the dynamic genetic architecture of maize plant growth and enhance ideotype-based maize breeding and prediction. © 2017 American Society of Plant Biologists. All Rights Reserved.

High-Throughput Phenotyping and QTL Mapping Reveals the Genetic Architecture of Maize Plant Growth1[OPEN

PubMed Central

Huang, Chenglong; Wu, Di; Qiao, Feng; Li, Wenqiang; Duan, Lingfeng; Wang, Ke; Xiao, Yingjie; Chen, Guoxing; Liu, Qian; Yang, Wanneng

2017-01-01

With increasing demand for novel traits in crop breeding, the plant research community faces the challenge of quantitatively analyzing the structure and function of large numbers of plants. A clear goal of high-throughput phenotyping is to bridge the gap between genomics and phenomics. In this study, we quantified 106 traits from a maize (Zea mays) recombinant inbred line population (n = 167) across 16 developmental stages using the automatic phenotyping platform. Quantitative trait locus (QTL) mapping with a high-density genetic linkage map, including 2,496 recombinant bins, was used to uncover the genetic basis of these complex agronomic traits, and 988 QTLs have been identified for all investigated traits, including three QTL hotspots. Biomass accumulation and final yield were predicted using a combination of dissected traits in the early growth stage. These results reveal the dynamic genetic architecture of maize plant growth and enhance ideotype-based maize breeding and prediction. PMID:28153923

Systematic reviews addressing microsurgical head and neck reconstruction.

PubMed

Momeni, Arash; Jacobson, Joshua Y; Lee, Gordon K

2015-01-01

Systematic reviews frequently form the basis for clinical decision making and guideline development. Yet, the quality of systematic reviews has been variable, thus raising concerns about the validity of their conclusions. In the current study, a quality analysis of systematic reviews was performed, addressing microsurgical head and neck reconstruction. A PubMed search was performed to identify all systematic reviews published up to and including December 2012 in 12 surgical journals. Two authors independently reviewed the literature and extracted data from the included reviews. Discrepancies were resolved by consensus. Quality assessment was performed using AMSTAR. The initial search retrieved 1020 articles. After screening titles and abstracts, 987 articles were excluded. Full-text review of the remaining 33 articles resulted in further exclusion of 18 articles, leaving 15 systematic reviews for final analysis. A marked increase in the number of published systematic reviews over time was noted (P = 0.07). The median AMSTAR score was 5, thus reflecting a "fair" quality. No evidence for improvement in methodological quality over time was noted. The trend to publish more systematic reviews in microsurgical head and neck reconstruction is encouraging. However, efforts are indicated to improve the methodological quality of systematic reviews. Familiarity with criteria of methodological quality is critical to ensure future improvements in the quality of systematic reviews conducted in microsurgery.

"Assessing the methodological quality of systematic reviews in radiation oncology: A systematic review".

PubMed

Hasan, Haroon; Muhammed, Taaha; Yu, Jennifer; Taguchi, Kelsi; Samargandi, Osama A; Howard, A Fuchsia; Lo, Andrea C; Olson, Robert; Goddard, Karen

2017-10-01

The objective of our study was to evaluate the methodological quality of systematic reviews and meta-analyses in Radiation Oncology. A systematic literature search was conducted for all eligible systematic reviews and meta-analyses in Radiation Oncology from 1966 to 2015. Methodological characteristics were abstracted from all works that satisfied the inclusion criteria and quality was assessed using the critical appraisal tool, AMSTAR. Regression analyses were performed to determine factors associated with a higher score of quality. Following exclusion based on a priori criteria, 410 studies (157 systematic reviews and 253 meta-analyses) satisfied the inclusion criteria. Meta-analyses were found to be of fair to good quality while systematic reviews were found to be of less than fair quality. Factors associated with higher scores of quality in the multivariable analysis were including primary studies consisting of randomized control trials, performing a meta-analysis, and applying a recommended guideline related to establishing a systematic review protocol and/or reporting. Systematic reviews and meta-analyses may introduce a high risk of bias if applied to inform decision-making based on AMSTAR. We recommend that decision-makers in Radiation Oncology scrutinize the methodological quality of systematic reviews and meta-analyses prior to assessing their utility to inform evidence-based medicine and researchers adhere to methodological standards outlined in validated guidelines when embarking on a systematic review. Copyright © 2017 Elsevier Ltd. All rights reserved.

Association between use of systematic reviews and national policy recommendations on screening newborn babies for rare diseases: systematic review and meta-analysis.

PubMed

Taylor-Phillips, Sian; Stinton, Chris; Ferrante di Ruffano, Lavinia; Seedat, Farah; Clarke, Aileen; Deeks, Jonathan J

2018-05-09

To understand whether international differences in recommendations of whether to screen for rare diseases using the newborn blood spot test might in part be explained by use of systematic review methods. Systematic review and meta-analysis. Website searches of 26 national screening organisations. Journal articles, papers, legal documents, presentations, conference abstracts, or reports relating to a national recommendation on whether to screen for any condition using the newborn blood spot test, with no restrictions on date or language. Two reviewers independently assessed whether the recommendation for or against screening included systematic reviews, and data on test accuracy, benefits of early detection, and potential harms of overdiagnosis. The odds of recommending screening according to the use of systematic review methods was estimated across conditions using meta-analysis. 93 reports were included that assessed 104 conditions across 14 countries, totalling 276 recommendations (units of analysis). Screening was favoured in 159 (58%) recommendations, not favoured in 98 (36%), and not recommended either way in 19 (7%). Only 60 (22%) of the recommendations included a systematic review. Use of a systematic review was associated with a reduced probability of screening being recommended (23/60 (38%) v 136/216 (63%), odds ratio 0.17, 95% confidence interval 0.07 to 0.43). Of the recommendations, evidence for test accuracy, benefits of early detection, and overdiagnosis was not considered in 115 (42%), 83 (30%), and 211 (76%), respectively. Using systematic review methods is associated with a reduced probability of screening being recommended. Many national policy reviews of screening for rare conditions using the newborn blood spot test do not assess the evidence on the key benefits and harms of screening. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Factor Analysis Methods and Validity Evidence: A Systematic Review of Instrument Development across the Continuum of Medical Education

ERIC Educational Resources Information Center

Wetzel, Angela Payne

2011-01-01

Previous systematic reviews indicate a lack of reporting of reliability and validity evidence in subsets of the medical education literature. Psychology and general education reviews of factor analysis also indicate gaps between current and best practices; yet, a comprehensive review of exploratory factor analysis in instrument development across…

Analysis of Wind Tunnel Polar Replicates Using the Modern Design of Experiments

NASA Technical Reports Server (NTRS)

Deloach, Richard; Micol, John R.

2010-01-01

The role of variance in a Modern Design of Experiments analysis of wind tunnel data is reviewed, with distinctions made between explained and unexplained variance. The partitioning of unexplained variance into systematic and random components is illustrated, with examples of the elusive systematic component provided for various types of real-world tests. The importance of detecting and defending against systematic unexplained variance in wind tunnel testing is discussed, and the random and systematic components of unexplained variance are examined for a representative wind tunnel data set acquired in a test in which a missile is used as a test article. The adverse impact of correlated (non-independent) experimental errors is described, and recommendations are offered for replication strategies that facilitate the quantification of random and systematic unexplained variance.

[Analysis of the implementation of Nursing Assistance Systematization in a rehabilitation unit].

PubMed

Neves, Rinaldo de Souza; Shimizu, Helena Eri

2010-01-01

This study seeks to analyze the execution of the Infirmary Attendance Systematization Nursing stages through an exploratory, qualitative and retrospective approach. The retrospective analysis took place using 25 medic reports containing 25 historical reports, 12 diagnosis reports, 100 prescriptions and 100 nursing evolution reports. The results demonstrated the many difficulties the nurses faced to make Nursing Assistance Systematization operational. Although all Nursing Assistance Systematization stages were accomplished - historical, diagnosis, prescription, evolution and nursing - it was verified a larger frequency in filling prescription and historical related forms and a lesser one related with evolution and diagnosis related forms. In short, Nursing Assistance Systematization procedures still are fragmentized, showing the need to reorganize this attendance methodology attendance, and, above all, to invest in continuous nursing training to improve the customer care services quality.

Functional classification of rice flanking sequence tagged genes using MapMan terms and global understanding on metabolic and regulatory pathways affected by dxr mutant having defects in light response.

PubMed

Chandran, Anil Kumar Nalini; Lee, Gang-Seob; Yoo, Yo-Han; Yoon, Ung-Han; Ahn, Byung-Ohg; Yun, Doh-Won; Kim, Jin-Hyun; Choi, Hong-Kyu; An, GynHeung; Kim, Tae-Ho; Jung, Ki-Hong

2016-12-01

Rice is one of the most important food crops for humans. To improve the agronomical traits of rice, the functions of more than 1,000 rice genes have been recently characterized and summarized. The completed, map-based sequence of the rice genome has significantly accelerated the functional characterization of rice genes, but progress remains limited in assigning functions to all predicted non-transposable element (non-TE) genes, estimated to number 37,000-41,000. The International Rice Functional Genomics Consortium (IRFGC) has generated a huge number of gene-indexed mutants by using mutagens such as T-DNA, Tos17 and Ds/dSpm. These mutants have been identified by 246,566 flanking sequence tags (FSTs) and cover 65 % (25,275 of 38,869) of the non-TE genes in rice, while the mutation ratio of TE genes is 25.7 %. In addition, almost 80 % of highly expressed non-TE genes have insertion mutations, indicating that highly expressed genes in rice chromosomes are more likely to have mutations by mutagens such as T-DNA, Ds, dSpm and Tos17. The functions of around 2.5 % of rice genes have been characterized, and studies have mainly focused on transcriptional and post-transcriptional regulation. Slow progress in characterizing the function of rice genes is mainly due to a lack of clues to guide functional studies or functional redundancy. These limitations can be partially solved by a well-categorized functional classification of FST genes. To create this classification, we used the diverse overviews installed in the MapMan toolkit. Gene Ontology (GO) assignment to FST genes supplemented the limitation of MapMan overviews. The functions of 863 of 1,022 known genes can be evaluated by current FST lines, indicating that FST genes are useful resources for functional genomic studies. We assigned 16,169 out of 29,624 FST genes to 34 MapMan classes, including major three categories such as DNA, RNA and protein. To demonstrate the MapMan application on FST genes, transcriptome analysis was done from a rice mutant of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) gene with FST. Mapping of 756 down-regulated genes in dxr mutants and their annotation in terms of various MapMan overviews revealed candidate genes downstream of DXR-mediating light signaling pathway in diverse functional classes such as the methyl-D-erythritol 4-phosphatepathway (MEP) pathway overview, photosynthesis, secondary metabolism and regulatory overview. This report provides a useful guide for systematic phenomics and further applications to enhance the key agronomic traits of rice.

Fried food and prostate cancer risk: systematic review and meta-analysis.

PubMed

Lippi, Giuseppe; Mattiuzzi, Camilla

2015-01-01

We performed systematic review and meta-analysis of published studies that investigated the potential association between fried food consumption and prostate cancer risk. Four case-control studies were finally selected for this systematic literature review, totaling 2579 cancer patients and 2277 matched controls. In two of these studies, the larger intake of fried food was associated with a 1.3- to 2.3-fold increased risk of prostate cancer, no significant association was found in another, whereas an inverse relationship was observed in the remaining. The meta-analysis of published data showed that larger intake of fried food was associated with a 35% (95% CI 17-57%) increased risk of prostate cancer. The results of this systematic literature review support the notion that larger intake of fried foods may have a role in increasing the risk of prostate cancer.

Pulsed Direct Current Electrospray: Enabling Systematic Analysis of Small Volume Sample by Boosting Sample Economy.

PubMed

Wei, Zhenwei; Xiong, Xingchuang; Guo, Chengan; Si, Xingyu; Zhao, Yaoyao; He, Muyi; Yang, Chengdui; Xu, Wei; Tang, Fei; Fang, Xiang; Zhang, Sichun; Zhang, Xinrong

2015-11-17

We had developed pulsed direct current electrospray ionization mass spectrometry (pulsed-dc-ESI-MS) for systematically profiling and determining components in small volume sample. Pulsed-dc-ESI utilized constant high voltage to induce the generation of single polarity pulsed electrospray remotely. This method had significantly boosted the sample economy, so as to obtain several minutes MS signal duration from merely picoliter volume sample. The elongated MS signal duration enable us to collect abundant MS(2) information on interested components in a small volume sample for systematical analysis. This method had been successfully applied for single cell metabolomics analysis. We had obtained 2-D profile of metabolites (including exact mass and MS(2) data) from single plant and mammalian cell, concerning 1034 components and 656 components for Allium cepa and HeLa cells, respectively. Further identification had found 162 compounds and 28 different modification groups of 141 saccharides in a single Allium cepa cell, indicating pulsed-dc-ESI a powerful tool for small volume sample systematical analysis.

The Internationalization of the Academic Library: A Systematic Review of 25 Years of Literature on International Students

ERIC Educational Resources Information Center

Click, Amanda B.; Wiley, Claire Walker; Houlihan, Meggan

2017-01-01

This study is a systematic review of the library and information science (LIS) literature related to international students and academic libraries. A systematic review involves the methodical collection and analysis of a body of literature and is growing in popularity in the LIS field. Three well-known LIS databases were systematically searched…

Cost-Utility Analysis of Screening Strategies for Diabetic Retinopathy in Korea.

PubMed

Kim, Sang-Won; Kang, Gil-Won

2015-12-01

This study involved a cost-utility analysis of early diagnosis and treatment of diabetic retinopathy depending on the screening strategy used. The four screening strategies evaluated were no screening, opportunistic examination, systematic fundus photography, and systematic examination by an ophthalmologists. Each strategy was evaluated in 10,000 adults aged 40 yr with newly diagnosed diabetes mellitus (hypothetical cohort). The cost of each strategy was estimated in the perspective of both payer and health care system. The utility was estimated using quality-adjusted life years (QALY). Incremental Cost Effectiveness Ratio (ICER) for the different screening strategies was analyzed. After exclusion of the weakly dominating opportunistic strategy, the ICER of systematic photography was 57,716,867 and that of systematic examination by ophthalmologists was 419,989,046 from the perspective of the healthcare system. According to the results, the systematic strategy is preferable to the opportunistic strategy from the perspective of both a payer and a healthcare system. Although systematic examination by ophthalmologists may have higher utility than systematic photography, it is associated with higher cost. The systematic photography is the best strategy in terms of cost-utility. However systematic examination by ophthalmologists can also be a suitable policy alternative, if the incremental cost is socially acceptable.

The search and selection for primary studies in systematic reviews published in dental journals indexed in MEDLINE was not fully reproducible.

PubMed

Faggion, Clovis Mariano; Huivin, Raquel; Aranda, Luisiana; Pandis, Nikolaos; Alarcon, Marco

2018-06-01

To evaluate whether the reporting of search strategies and the primary study selection process in dental systematic reviews is reproducible. A survey of systematic reviews published in MEDLINE-indexed dental journals from June 2015 to June 2016 was conducted. Study selection was performed independently by two authors, and the reproducibility of the selection process was assessed using a tool consisting of 12 criteria. Regression analyses were implemented to evaluate any associations between degrees of reporting (measured by the number of items positively answered) and journal impact factor (IF), presence of meta-analysis, and number of citations of the systematic review in Google Scholar. Five hundred and thirty systematic reviews were identified. Following our 12 criteria, none of the systematic reviews had complete reporting of the search strategies and selection process. Eight (1.5%) systematic reviews reported the list of excluded articles (with reasons for exclusion) after title and abstract assessment. Systematic reviews with more positive answers to the criteria were significantly associated with higher journal IF, number of citations, and inclusion of meta-analysis. Search strategies and primary study selection process in systematic reviews published in MEDLINE-indexed dental journals may not be fully reproducible. Copyright © 2018 Elsevier Inc. All rights reserved.

Reporting and handling missing outcome data in mental health: a systematic review of Cochrane systematic reviews and meta-analyses.

PubMed

Spineli, Loukia M; Pandis, Nikolaos; Salanti, Georgia

2015-06-01

The purpose of the study was to provide empirical evidence about the reporting of methodology to address missing outcome data and the acknowledgement of their impact in Cochrane systematic reviews in the mental health field. Systematic reviews published in the Cochrane Database of Systematic Reviews after January 1, 2009 by three Cochrane Review Groups relating to mental health were included. One hundred ninety systematic reviews were considered. Missing outcome data were present in at least one included study in 175 systematic reviews. Of these 175 systematic reviews, 147 (84%) accounted for missing outcome data by considering a relevant primary or secondary outcome (e.g., dropout). Missing outcome data implications were reported only in 61 (35%) systematic reviews and primarily in the discussion section by commenting on the amount of the missing outcome data. One hundred forty eligible meta-analyses with missing data were scrutinized. Seventy-nine (56%) of them had studies with total dropout rate between 10 and 30%. One hundred nine (78%) meta-analyses reported to have performed intention-to-treat analysis by including trials with imputed outcome data. Sensitivity analysis for incomplete outcome data was implemented in less than 20% of the meta-analyses. Reporting of the techniques for handling missing outcome data and their implications in the findings of the systematic reviews are suboptimal. Copyright © 2014 John Wiley & Sons, Ltd.

Methodological quality of systematic reviews on influenza vaccination.

PubMed

Remschmidt, Cornelius; Wichmann, Ole; Harder, Thomas

2014-03-26

There is a growing body of evidence on the risks and benefits of influenza vaccination in various target groups. Systematic reviews are of particular importance for policy decisions. However, their methodological quality can vary considerably. To investigate the methodological quality of systematic reviews on influenza vaccination (efficacy, effectiveness, safety) and to identify influencing factors. A systematic literature search on systematic reviews on influenza vaccination was performed, using MEDLINE, EMBASE and three additional databases (1990-2013). Review characteristics were extracted and the methodological quality of the reviews was evaluated using the assessment of multiple systematic reviews (AMSTAR) tool. U-test, Kruskal-Wallis test, chi-square test, and multivariable linear regression analysis were used to assess the influence of review characteristics on AMSTAR-score. Fourty-six systematic reviews fulfilled the inclusion criteria. Average methodological quality was high (median AMSTAR-score: 8), but variability was large (AMSTAR range: 0-11). Quality did not differ significantly according to vaccination target group. Cochrane reviews had higher methodological quality than non-Cochrane reviews (p=0.001). Detailed analysis showed that this was due to better study selection and data extraction, inclusion of unpublished studies, and better reporting of study characteristics (all p<0.05). In the adjusted analysis, no other factor, including industry sponsorship or journal impact factor had an influence on AMSTAR score. Systematic reviews on influenza vaccination showed large differences regarding their methodological quality. Reviews conducted by the Cochrane collaboration were of higher quality than others. When using systematic reviews to guide the development of vaccination recommendations, the methodological quality of a review in addition to its content should be considered. Copyright © 2014 Elsevier Ltd. All rights reserved.

CrossFit Overview: Systematic Review and Meta-analysis.

PubMed

Claudino, João Gustavo; Gabbett, Tim J; Bourgeois, Frank; Souza, Helton de Sá; Miranda, Rafael Chagas; Mezêncio, Bruno; Soncin, Rafael; Cardoso Filho, Carlos Alberto; Bottaro, Martim; Hernandez, Arnaldo Jose; Amadio, Alberto Carlos; Serrão, Julio Cerca

2018-02-26

CrossFit is recognized as one of the fastest growing high-intensity functional training modes in the world. However, scientific data regarding the practice of CrossFit is sparse. Therefore, the objective of this study is to analyze the findings of scientific literature related to CrossFit via systematic review and meta-analysis. Systematic searches of the PubMed, Web of Science, Scopus, Bireme/MedLine, and SciELO online databases were conducted for articles reporting the effects of CrossFit training. The systematic review followed the PRISMA guidelines. The Oxford Levels of Evidence was used for all included articles, and only studies that investigated the effects of CrossFit as a training program were included in the meta-analysis. For the meta-analysis, effect sizes (ESs) with 95% confidence interval (CI) were calculated and heterogeneity was assessed using a random-effects model. Thirty-one articles were included in the systematic review and four were included in the meta-analysis. However, only two studies had a high level of evidence at low risk of bias. Scientific literature related to CrossFit has reported on body composition, psycho-physiological parameters, musculoskeletal injury risk, life and health aspects, and psycho-social behavior. In the meta-analysis, significant results were not found for any variables. The current scientific literature related to CrossFit has few studies with high level of evidence at low risk of bias. However, preliminary data has suggested that CrossFit practice is associated with higher levels of sense of community, satisfaction, and motivation.

Vitamin D and depression: a systematic review and meta-analysis comparing studies with and without biological flaws.

PubMed

Spedding, Simon

2014-04-11

Efficacy of Vitamin D supplements in depression is controversial, awaiting further literature analysis. Biological flaws in primary studies is a possible reason meta-analyses of Vitamin D have failed to demonstrate efficacy. This systematic review and meta-analysis of Vitamin D and depression compared studies with and without biological flaws. The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The literature search was undertaken through four databases for randomized controlled trials (RCTs). Studies were critically appraised for methodological quality and biological flaws, in relation to the hypothesis and study design. Meta-analyses were performed for studies according to the presence of biological flaws. The 15 RCTs identified provide a more comprehensive evidence-base than previous systematic reviews; methodological quality of studies was generally good and methodology was diverse. A meta-analysis of all studies without flaws demonstrated a statistically significant improvement in depression with Vitamin D supplements (+0.78 CI +0.24, +1.27). Studies with biological flaws were mainly inconclusive, with the meta-analysis demonstrating a statistically significant worsening in depression by taking Vitamin D supplements (-1.1 CI -0.7, -1.5). Vitamin D supplementation (≥800 I.U. daily) was somewhat favorable in the management of depression in studies that demonstrate a change in vitamin levels, and the effect size was comparable to that of anti-depressant medication.

Processed red meat intake and risk of COPD: A systematic review and dose-response meta-analysis of prospective cohort studies.

PubMed

Salari-Moghaddam, Asma; Milajerdi, Alireza; Larijani, Bagher; Esmaillzadeh, Ahmad

2018-06-01

No earlier study has summarized findings from previous publications on processed red meat intake and risk of Chronic Obstructive Pulmonary Disease (COPD). This systematic review and meta-analysis was conducted to examine the association between processed red meat intake and COPD risk. We searched in PubMed/Medline, ISI Web of Knowledge, Scopus, EMBASE and Google Scholar up to April 2018 to identify relevant studies. Prospective cohort studies that considered processed red meat as the exposure variable and COPD as the main outcome variable or as one of the outcomes were included in the systematic review. Publications in which hazard ratios (HRs) were reported as effect size were included in the meta-analysis. Finally, five cohort studies were considered in this systematic review and meta-analysis. In total, 289,952 participants, including 8338 subjects with COPD, aged ≥27 years were included in the meta-analysis. These studies were from Sweden and the US. Linear dose response meta-analysis revealed that each 50 gr/week increase in processed red meat intake was associated with 8% higher risk of COPD (HR: 1.08; 95% CI: 1.03, 1.13). There was an evidence of non-linear association between processed red meat intake and risk of COPD (P < 0.001). In this systematic review and meta-analysis, we found a significant positive association between processed red meat intake and risk of COPD. CRD42017077971. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Systematic review and meta-analysis: tools for the information age.

PubMed

Weatherall, Mark

2017-11-01

The amount of available biomedical information is vast and growing. Natural limitations of the way clinicians and researchers approach this treasure trove of information comprise difficulties locating the information, and once located, cognitive biases may lead to inappropriate use of the information. Systematic reviews and meta-analyses represent important tools in the information age to improve knowledge and action. Systematic reviews represent a census approach to identifying literature to avoid non-response bias. They are a necessary prelude to producing combined quantitative summaries of associations or treatment effects. Meta-analysis comprises the arithmetical techniques for producing combined summaries from individual study reports. Careful, thoughtful and rigorous use of these tools is likely to enhance knowledge and action. Use of standard guidelines, such as the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, or embedding these activities within collaborative groups such as the Cochrane Collaboration, are likely to lead to more useful systematic review and meta-analysis reporting. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Using qualitative comparative analysis in a systematic review of a complex intervention.

PubMed

Kahwati, Leila; Jacobs, Sara; Kane, Heather; Lewis, Megan; Viswanathan, Meera; Golin, Carol E

2016-05-04

Systematic reviews evaluating complex interventions often encounter substantial clinical heterogeneity in intervention components and implementation features making synthesis challenging. Qualitative comparative analysis (QCA) is a non-probabilistic method that uses mathematical set theory to study complex phenomena; it has been proposed as a potential method to complement traditional evidence synthesis in reviews of complex interventions to identify key intervention components or implementation features that might explain effectiveness or ineffectiveness. The objective of this study was to describe our approach in detail and examine the suitability of using QCA within the context of a systematic review. We used data from a completed systematic review of behavioral interventions to improve medication adherence to conduct two substantive analyses using QCA. The first analysis sought to identify combinations of nine behavior change techniques/components (BCTs) found among effective interventions, and the second analysis sought to identify combinations of five implementation features (e.g., agent, target, mode, time span, exposure) found among effective interventions. For each substantive analysis, we reframed the review's research questions to be designed for use with QCA, calibrated sets (i.e., transformed raw data into data used in analysis), and identified the necessary and/or sufficient combinations of BCTs and implementation features found in effective interventions. Our application of QCA for each substantive analysis is described in detail. We extended the original review findings by identifying seven combinations of BCTs and four combinations of implementation features that were sufficient for improving adherence. We found reasonable alignment between several systematic review steps and processes used in QCA except that typical approaches to study abstraction for some intervention components and features did not support a robust calibration for QCA. QCA was suitable for use within a systematic review of medication adherence interventions and offered insights beyond the single dimension stratifications used in the original completed review. Future prospective use of QCA during a review is needed to determine the optimal way to efficiently integrate QCA into existing approaches to evidence synthesis of complex interventions.

Indirect health costs in ulcerative colitis and Crohn's disease: a systematic review and meta-analysis.

PubMed

Kawalec, Paweł; Malinowski, Krzysztof Piotr

2015-04-01

The aim of this systematic review was to collect all current data on indirect costs related to inflammatory bowel disease as well as assessing homogeneity and comparability, and conducting a meta-analysis. Costs were collected using databases from Medline, Embase and Centre for Reviews and Dissemination databases, then average annual cost per patient was calculated and expressed in 2013-rate USD using the consumer price index and purchasing power parity (scenario 1) and then adjusted to specific gross domestic product (scenario 2) to make them comparable. The studies were then included in quantitative synthesis using the meta-analysis and bootstrap methods. This systematic review was carried out and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. From 18 publications, overall annual indirect costs per patient as a result of the quantitative synthesis among all studies eligible for meta-analysis ranged from US$2425.01-US$9622.15 depending on the scenario and model used for analysis. The cost of presenteeism was assessed in only two studies. Considering heterogeneity among all identified studies random-effect model presented the most accurate results of meta-analysis equal to US$7189.27 and US$9622.15 per patient per year for scenario 1 and scenario 2, respectively. This systematic review revealed the existence of a relatively small number of studies that reported on the great economic burden of the disease upon society. A great variety of methodologies and cost components resulted in a very large discrepancy in indirect costs and made meta-analysis difficult to perform, so two scenarios were considered and meta-analysis conducted in subgroups to make data more comparable.

Dynamic Geometry Software Improves Mathematical Achievement: Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Chan, Kan Kan; Leung, Siu Wai

2014-01-01

Dynamic geometry software (DGS) aims to enhance mathematics education. This systematic review and meta-analysis evaluated the quasi-experimental studies on the effectiveness of DGS-based instruction in improving students' mathematical achievement. Research articles published between 1990 and 2013 were identified from major databases according to a…

Developing a Systematic Patent Search Training Program

ERIC Educational Resources Information Center

Zhang, Li

2009-01-01

This study aims to develop a systematic patent training program using patent analysis and citation analysis techniques applied to patents held by the University of Saskatchewan. The results indicate that the target audience will be researchers in life sciences, and aggregated patent database searching and advanced search techniques should be…

The Campbell Collaboration's Systematic Review and Meta-Analysis Online Training Videos

ERIC Educational Resources Information Center

Polanin, Joshua R.; Pigott, Terri D.

2013-01-01

Systematic reviews and meta-analysis are techniques for synthesizing primary empirical studies to produce a summary of effects. To facilitate this goal, the Campbell Collaboration (C2) supports reviews within the disciplines of crime and justice, education, international development, and social welfare. At the annual Campbell Colloquium, experts…

Is Neonatal Jaundice Associated with Autism Spectrum Disorders: A Systematic Review

ERIC Educational Resources Information Center

Amin, Sanjiv B.; Smith, Tristram; Wang, Hongyue

2011-01-01

Using guidelines of the Meta-analysis of Observational Studies in Epidemiology Group, we systematically reviewed the literature on neonatal jaundice (unconjugated hyperbilirubinemia) and Autism Spectrum Disorder (ASD) in term and preterm infants. Thirteen studies were included in a meta-analysis. Most used retrospective matched case-control…

Current state of ethics literature synthesis: a systematic review of reviews.

PubMed

Mertz, Marcel; Kahrass, Hannes; Strech, Daniel

2016-10-03

Modern standards for evidence-based decision making in clinical care and public health still rely solely on eminence-based input when it comes to normative ethical considerations. Manuals for clinical guideline development or health technology assessment (HTA) do not explain how to search, analyze, and synthesize relevant normative information in a systematic and transparent manner. In the scientific literature, however, systematic or semi-systematic reviews of ethics literature already exist, and scholarly debate on their opportunities and limitations has recently bloomed. A systematic review was performed of all existing systematic or semi-systematic reviews for normative ethics literature on medical topics. The study further assessed how these reviews report on their methods for search, selection, analysis, and synthesis of ethics literature. We identified 84 reviews published between 1997 and 2015 in 65 different journals and demonstrated an increasing publication rate for this type of review. While most reviews reported on different aspects of search and selection methods, reporting was much less explicit for aspects of analysis and synthesis methods: 31 % did not fulfill any criteria related to the reporting of analysis methods; for example, only 25 % of the reviews reported the ethical approach needed to analyze and synthesize normative information. While reviews of ethics literature are increasingly published, their reporting quality for analysis and synthesis of normative information should be improved. Guiding questions are: What was the applied ethical approach and technical procedure for identifying and extracting the relevant normative information units? What method and procedure was employed for synthesizing normative information? Experts and stakeholders from bioethics, HTA, guideline development, health care professionals, and patient organizations should work together to further develop this area of evidence-based health care.

Elucidation of the Metabolic Network of Helicobacter pylori J99 and Malaysian Clinical Strains by Phenotype Microarray.

PubMed

Lee, Woon Ching; Goh, Khean Lee; Loke, Mun Fai; Vadivelu, Jamuna

2017-02-01

Helicobacter pylori colonizes almost half of the human population worldwide. H. pylori strains are genetically diverse, and the specific genotypes are associated with various clinical manifestations including gastric adenocarcinoma, peptic ulcer disease (PUD), and nonulcer dyspepsia (NUD). However, our current knowledge of the H. pylori metabolism is limited. To understand the metabolic differences among H. pylori strains, we investigated four Malaysian H. pylori clinical strains, which had been previously sequenced, and a standard strain, H. pylori J99, at the phenotypic level. The phenotypes of the H. pylori strains were profiled using the Biolog Phenotype Microarray system to corroborate genomic data. We initiated the analyses by predicting carbon and nitrogen metabolic pathways from the H. pylori genomic data from the KEGG database. Biolog PM aided the validation of the prediction and provided a more intensive analysis of the H. pylori phenomes. We have identified a core set of metabolic nutrient sources that was utilized by all strains tested and another set that was differentially utilized by only the local strains. Pentose sugars are the preferred carbon nutrients utilized by H. pylori. The amino acids l-aspartic acid, d-alanine, and l-asparagine serve as both carbon and nitrogen sources in the metabolism of the bacterium. The phenotypic profile based on this study provides a better understanding on the survival of H. pylori in its natural host. Our data serve as a foundation for future challenges in correlating interstrain metabolic differences in H. pylori. © 2016 The Authors. Helicobacter Published by John Wiley & Sons Ltd.

Evaluating statistical approaches to leverage large clinical datasets for uncovering therapeutic and adverse medication effects.

PubMed

Choi, Leena; Carroll, Robert J; Beck, Cole; Mosley, Jonathan D; Roden, Dan M; Denny, Joshua C; Van Driest, Sara L

2018-04-18

Phenome-wide association studies (PheWAS) have been used to discover many genotype-phenotype relationships and have the potential to identify therapeutic and adverse drug outcomes using longitudinal data within electronic health records (EHRs). However, the statistical methods for PheWAS applied to longitudinal EHR medication data have not been established. In this study, we developed methods to address two challenges faced with reuse of EHR for this purpose: confounding by indication, and low exposure and event rates. We used Monte Carlo simulation to assess propensity score (PS) methods, focusing on two of the most commonly used methods, PS matching and PS adjustment, to address confounding by indication. We also compared two logistic regression approaches (the default of Wald vs. Firth's penalized maximum likelihood, PML) to address complete separation due to sparse data with low exposure and event rates. PS adjustment resulted in greater power than propensity score matching, while controlling Type I error at 0.05. The PML method provided reasonable p-values, even in cases with complete separation, with well controlled Type I error rates. Using PS adjustment and the PML method, we identify novel latent drug effects in pediatric patients exposed to two common antibiotic drugs, ampicillin and gentamicin. R packages PheWAS and EHR are available at https://github.com/PheWAS/PheWAS and at CRAN (https://www.r-project.org/), respectively. The R script for data processing and the main analysis is available at https://github.com/choileena/EHR. leena.choi@vanderbilt.edu. Supplementary data are available at Bioinformatics online.

Towards first principle medical diagnostics: on the importance of disease-disease and sign-sign interactions

NASA Astrophysics Data System (ADS)

Ramezanpour, Abolfazl; Mashaghi, Alireza

2017-07-01

A fundamental problem in medicine and biology is to assign states, e.g. healthy or diseased, to cells, organs or individuals. State assignment or making a diagnosis is often a nontrivial and challenging process and, with the advent of omics technologies, the diagnostic challenge is becoming more and more serious. The challenge lies not only in the increasing number of measured properties and dynamics of the system (e.g. cell or human body) but also in the co-evolution of multiple states and overlapping properties, and degeneracy of states. We develop, from first principles, a generic rational framework for state assignment in cell biology and medicine, and demonstrate its applicability with a few simple theoretical case studies from medical diagnostics. We show how disease-related statistical information can be used to build a comprehensive model that includes the relevant dependencies between clinical and laboratory findings (signs) and diseases. In particular, we include disease-disease and sign-sign interactions and study how one can infer the probability of a disease in a patient with given signs. We perform comparative analysis with simple benchmark models to check the performances of our models. We find that including interactions can significantly change the statistical importance of the signs and diseases. This first principles approach, as we show, facilitates the early diagnosis of disease by taking interactions into accounts, and enables the construction of consensus diagnostic flow charts. Additionally, we envision that our approach will find applications in systems biology, and in particular, in characterizing the phenome via the metabolome, the proteome, the transcriptome, and the genome.

Determining which phenotypes underlie a pleiotropic signal

PubMed Central

Majumdar, Arunabha; Haldar, Tanushree; Witte, John S.

2016-01-01

Discovering pleiotropic loci is important to understand the biological basis of seemingly distinct phenotypes. Most methods for assessing pleiotropy only test for the overall association between genetic variants and multiple phenotypes. To determine which specific traits are pleiotropic, we evaluate via simulation and application three different strategies. The first is model selection techniques based on the inverse regression of genotype on phenotypes. The second is a subset-based meta-analysis ASSET [Bhattacharjee et al., 2012], which provides an optimal subset of non-null traits. And the third is a modified Benjamini-Hochberg (B-H) procedure of controlling the expected false discovery rate [Benjamini and Hochberg, 1995] in the framework of phenome-wide association study. From our simulations we see that an inverse regression based approach MultiPhen [O’Reilly et al., 2012] is more powerful than ASSET for detecting overall pleiotropic association, except for when all the phenotypes are associated and have genetic effects in the same direction. For determining which specific traits are pleiotropic, the modified B-H procedure performs consistently better than the other two methods. The inverse regression based selection methods perform competitively with the modified B-H procedure only when the phenotypes are weakly correlated. The efficiency of ASSET is observed to lie below and in between the efficiency of the other two methods when the traits are weakly and strongly correlated, respectively. In our application to a large GWAS, we find that the modified B-H procedure also performs well, indicating that this may be an optimal approach for determining the traits underlying a pleiotropic signal. PMID:27238845

Ictal fear: Associations with age, gender, and other experiential phenomena.

PubMed

Chong, Derek J; Dugan, Patricia

2016-09-01

The aim of this study was to determine the relationship of fear to other auras and to gender and age using a large database. The Epilepsy Phenome/Genome Project (EPGP) is a multicenter, multicontinental cross-sectional study in which ictal symptomatology and other data were ascertained in a standardized series of questionnaires then corroborated by epilepsy specialists. Auras were classified into subgroups of symptoms, with ictal fear, panic, or anxiety as a single category. Of 536 participants with focal epilepsy, 72 were coded as having ictal fear/panic/anxiety. Reviewing raw patient responses, 12 participants were deemed not to have fear, and 24 had inadequate data, leaving 36 (7%) of 512 with definite ictal fear. In univariate analyses, fear was significantly associated with auras historically considered temporal lobe in origin, including cephalic, olfactory, and visceral complaints; déjà vu; and derealization. On both univariate and multivariate stepwise analyses, fear was associated with jamais vu and auras with cardiac symptoms, dyspnea, and chest tightening. Expressive aphasia was associated with fear on univariate analysis only, but the general category of aphasias was associated with fear only in the multivariate model. There was no age or gender relationship with fear when compared to the overall population with focal epilepsy that was studied under the EPGP. Patients with ictal fear were more likely to have a right hemisphere seizure focus. Ictal fear was strongly associated with other auras considered to originate from the limbic system. No relationship of fear with age or gender was observed. Copyright © 2016 Elsevier Inc. All rights reserved.

Biological processes modulating longevity across primates: a phylogenetic genome-phenome analysis.

PubMed

Muntané, Gerard; Farré, Xavier; Antonio Rodríguez, Juan; Pegueroles, Cinta; Hughes, David A; de Magalhães, João Pedro; Gabaldón, Toni; Navarro, Arcadi

2018-05-21

Aging is a complex process affecting different species and individuals in different ways. Comparing genetic variation across species with their aging phenotypes will help understanding the molecular basis of aging and longevity. Although most studies on aging have so far focused on short-lived model organisms, recent comparisons of genomic, transcriptomic, and metabolomic data across lineages with different lifespans are unveiling molecular signatures associated with longevity. Here, we examine the relationship between genomic variation and maximum lifespan (MLS) across primate species. We used two different approaches. First, we searched for parallel amino acid mutations that co-occur with increases in longevity across the primate linage. Twenty-five such amino acid variants were identified, several of which have been previously reported by studies with different experimental setups and in different model organisms. The genes harboring these mutations are mainly enriched in functional categories such as Wound Healing, Blood Coagulation and Cardiovascular Disorders. We demonstrate that these pathways are highly enriched for pleiotropic effects, as predicted by the Antagonistic Pleiotropy (AP) theory of aging. A second approach was focused on changes in rates of protein evolution across the primate phylogeny. Using the Phylogenetic Generalized Least Squares (PGLS) we show that some genes exhibit strong correlations between their evolutionary rates and longevity-associated traits. These include genes in the Sphingosine 1-phosphate pathway, PI3K signaling and the Thrombin/protease-activated receptor pathway, among other cardiovascular processes. Together, these results shed light into human senescence patterns and underscore the power of comparative genomics to identify pathways related to aging and longevity.

FPGA accelerator for protein secondary structure prediction based on the GOR algorithm

PubMed Central

2011-01-01

Background Protein is an important molecule that performs a wide range of functions in biological systems. Recently, the protein folding attracts much more attention since the function of protein can be generally derived from its molecular structure. The GOR algorithm is one of the most successful computational methods and has been widely used as an efficient analysis tool to predict secondary structure from protein sequence. However, the execution time is still intolerable with the steep growth in protein database. Recently, FPGA chips have emerged as one promising application accelerator to accelerate bioinformatics algorithms by exploiting fine-grained custom design. Results In this paper, we propose a complete fine-grained parallel hardware implementation on FPGA to accelerate the GOR-IV package for 2D protein structure prediction. To improve computing efficiency, we partition the parameter table into small segments and access them in parallel. We aggressively exploit data reuse schemes to minimize the need for loading data from external memory. The whole computation structure is carefully pipelined to overlap the sequence loading, computing and back-writing operations as much as possible. We implemented a complete GOR desktop system based on an FPGA chip XC5VLX330. Conclusions The experimental results show a speedup factor of more than 430x over the original GOR-IV version and 110x speedup over the optimized version with multi-thread SIMD implementation running on a PC platform with AMD Phenom 9650 Quad CPU for 2D protein structure prediction. However, the power consumption is only about 30% of that of current general-propose CPUs. PMID:21342582

In Pursuit of Neurophenotypes: The Consequences of Having Autism and a Big Brain

PubMed Central

Amaral, David G.; Li, Deana; Libero, Lauren; Solomon, Marjorie; Van de Water, Judy; Mastergeorge, Ann; Naigles, Letitia; Rogers, Sally; Nordahl, Christine Wu

2017-01-01

A consensus has emerged that despite common core features, autism spectrum disorder (ASD) has multiple etiologies and various genetic and biological characteristics. The fact that there are likely to be subtypes of ASD has complicated attempts to develop effective therapies. The UC Davis MIND Institute Autism Phenome Project is a longitudinal, multidisciplinary analysis of children with autism and age-matched typically developing controls; nearly 400 families are participating in this study. The overarching goal is to gather sufficient biological, medical, and behavioral data to allow definition of clinically meaningful subtypes of ASD. One reasonable hypothesis is that different subtypes of autism will demonstrate different patterns of altered brain organization or development i.e., different neurophenotypes. In this Commentary, we discuss one neurophenotype that is defined by megalencephaly, or having brain size that is large and disproportionate to body size. We have found that 15% of the boys with autism demonstrate this neurophenotype, though it is far less common in girls. We review behavioral and medical characteristics of the large-brained group of boys with autism in comparison to those with typically sized brains. While brain size in typically developing individuals is positively correlated with cognitive function, the children with autism and larger brains have more severe disabilities and poorer prognosis. This research indicates that phenotyping in autism, like genotyping, requires a very substantial cohort of subjects. Moreover, since brain and behavior relationships may emerge at different times during development, this effort highlights the need for longitudinal analyses to carry out meaningful phenotyping. PMID:28239961

Does cross-generational epigenetic inheritance contribute to cultural continuity?

PubMed Central

Pembrey, Marcus E

2018-01-01

Abstract Human studies of cross-generational epigenetic inheritance have to consider confounding by social patterning down the generations, often referred to as ‘cultural inheritance’. This raises the question to what extent is ‘cultural inheritance’ itself epigenetically mediated rather than just learnt. Human studies of non-genetic inheritance have demonstrated that, beyond foetal life, experiences occurring in mid-childhood before puberty are the most likely to be associated with cross-generational responses in the next generation(s). It is proposed that cultural continuity is played out along the axis, or ‘payoff’, between responsiveness and stability. During the formative years of childhood a stable family and/or home permits small children to explore and thereby learn. To counter disruptions to this family home ideal, cultural institutions such as local schools, religious centres and market places emerged to provide ongoing stability, holding the received wisdom of the past in an accessible state. This cultural support allows the growing child to freely indulge their responsiveness. Some of these prepubertal experiences induce epigenetic responses that also transfer molecular signals to the gametes through which they contribute to the conception of future offspring. In parallel co-evolution with growing cultural support for increasing responsiveness, ‘runaway’ responsiveness is countered by the positive selection of genetic variants that dampen responsiveness. Testing these ideas within longitudinal multigenerational cohorts will need information on ancestors/parents’ own communities and experiences (Exposome scans) linked to ongoing Phenome scans on grandchildren; coupled with epigenome analysis, metastable epialleles and DNA methylation age. Interactions with genetic variants affecting responsiveness should help inform the broad hypothesis. PMID:29732169

Does cross-generational epigenetic inheritance contribute to cultural continuity?

PubMed

Pembrey, Marcus E

2018-04-01

Human studies of cross-generational epigenetic inheritance have to consider confounding by social patterning down the generations, often referred to as 'cultural inheritance'. This raises the question to what extent is 'cultural inheritance' itself epigenetically mediated rather than just learnt. Human studies of non-genetic inheritance have demonstrated that, beyond foetal life, experiences occurring in mid-childhood before puberty are the most likely to be associated with cross-generational responses in the next generation(s). It is proposed that cultural continuity is played out along the axis, or 'payoff', between responsiveness and stability. During the formative years of childhood a stable family and/or home permits small children to explore and thereby learn. To counter disruptions to this family home ideal, cultural institutions such as local schools, religious centres and market places emerged to provide ongoing stability, holding the received wisdom of the past in an accessible state. This cultural support allows the growing child to freely indulge their responsiveness. Some of these prepubertal experiences induce epigenetic responses that also transfer molecular signals to the gametes through which they contribute to the conception of future offspring. In parallel co-evolution with growing cultural support for increasing responsiveness, 'runaway' responsiveness is countered by the positive selection of genetic variants that dampen responsiveness. Testing these ideas within longitudinal multigenerational cohorts will need information on ancestors/parents' own communities and experiences (Exposome scans) linked to ongoing Phenome scans on grandchildren; coupled with epigenome analysis, metastable epialleles and DNA methylation age. Interactions with genetic variants affecting responsiveness should help inform the broad hypothesis.

Ethnic variation of genetic (idiopathic) generalized epilepsy in Malaysia.

PubMed

Lim, Kheng Seang; Ng, Ching Ching; Chan, Chung Kin; Foo, Wee Shean; Low, Joyce Siew Yong; Tan, Chong Tin

2017-02-01

Ethnic variation in epilepsy classification was reported in the Epilepsy Phenome/Genome Project. This study aimed to determine the ethnic variation in the prevalence of genetic (idiopathic) generalized epilepsy (GGE) and GGE with family history in a multi-ethnic Asian population in Malaysia. In this cross-sectional study, 392 patients with a clinical diagnosis of GGE were recruited in the neurology outpatient clinic, University of Malaya Medical Centre (UMMC), from January 2011 till April 2016. In our epilepsy cohort (n=2100), 18.7% were diagnosed to have GGE. Of those, 28.6% >(N=112) had family history of epilepsy with a mean age of seizure onset of 16.5 years old, and 42.0% had myoclonic seizures (N=47). The lifetime prevalence of epilepsy among first-degree relative of those with GGE and positive family history was 15.0%. Analysis according to ethnicity showed that Malaysian Chinese had the lowest percentage of GGE among those with epilepsy (12.3%), as compared with Indian and Malay (25.3% and 21.3%, p<0.001). In addition, 32.1% of these Indian patients with GGE had positive family history, which is more than the Malay (26.4%) and Chinese (27.5%) ethnic groups. Consanguineous marriage was noted in 5 Indian families with positive family history (9.6%). There was ethnic variation in the prevalence of GGE, whereby the Malaysian Chinese had the lowest percentage of GGE as compared with Indian and Malay. A substantial proportion of GGE had positive family history among the three ethnics groups. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Systematic reviews addressing identified health policy priorities in Eastern Mediterranean countries: a situational analysis.

PubMed

El-Jardali, Fadi; Akl, Elie A; Karroum, Lama Bou; Kdouh, Ola; Akik, Chaza; Fadlallah, Racha; Hammoud, Rawan

2014-08-20

Systematic reviews can offer policymakers and stakeholders concise, transparent, and relevant evidence pertaining to pressing policy priorities to help inform the decision-making process. The production and the use of systematic reviews are specifically limited in the Eastern Mediterranean region. The extent to which published systematic reviews address policy priorities in the region is still unknown. This situational analysis exercise aims at assessing the extent to which published systematic reviews address policy priorities identified by policymakers and stakeholders in Eastern Mediterranean region countries. It also provides an overview about the state of systematic review production in the region and identifies knowledge gaps. We conducted a systematic search of the Health System Evidence database to identify published systematic reviews on policy-relevant priorities pertaining to the following themes: human resources for health, health financing, the role of the non-state sector, and access to medicine. Priorities were identified from two priority-setting exercises conducted in the region. We described the distribution of these systematic reviews across themes, sub-themes, authors' affiliations, and countries where included primary studies were conducted. Out of the 1,045 systematic reviews identified in Health System Evidence on selected themes, a total of 200 systematic reviews (19.1%) addressed the priorities from the Eastern Mediterranean region. The theme with the largest number of systematic reviews included was human resources for health (115) followed by health financing (33), access to medicine (27), and role of the non-state sector (25). Authors based in the region produced only three systematic reviews addressing regional priorities (1.5%). Furthermore, no systematic review focused on the Eastern Mediterranean region. Primary studies from the region had limited contribution to systematic reviews; 17 systematic reviews (8.5%) included primary studies conducted in the region. There are still gaps in the production of systematic reviews addressing policymakers' and stakeholders' priorities in the Eastern Mediterranean region. Efforts should be directed towards better aligning systematic review production with policy needs and priorities. Study findings can inform the agendas of researchers, research institutions, and international funding agencies of priority areas where systematic reviews are required.

Systematic reviews addressing identified health policy priorities in Eastern Mediterranean countries: a situational analysis

PubMed Central

2014-01-01

Background Systematic reviews can offer policymakers and stakeholders concise, transparent, and relevant evidence pertaining to pressing policy priorities to help inform the decision-making process. The production and the use of systematic reviews are specifically limited in the Eastern Mediterranean region. The extent to which published systematic reviews address policy priorities in the region is still unknown. This situational analysis exercise aims at assessing the extent to which published systematic reviews address policy priorities identified by policymakers and stakeholders in Eastern Mediterranean region countries. It also provides an overview about the state of systematic review production in the region and identifies knowledge gaps. Methods We conducted a systematic search of the Health System Evidence database to identify published systematic reviews on policy-relevant priorities pertaining to the following themes: human resources for health, health financing, the role of the non-state sector, and access to medicine. Priorities were identified from two priority-setting exercises conducted in the region. We described the distribution of these systematic reviews across themes, sub-themes, authors’ affiliations, and countries where included primary studies were conducted. Results Out of the 1,045 systematic reviews identified in Health System Evidence on selected themes, a total of 200 systematic reviews (19.1%) addressed the priorities from the Eastern Mediterranean region. The theme with the largest number of systematic reviews included was human resources for health (115) followed by health financing (33), access to medicine (27), and role of the non-state sector (25). Authors based in the region produced only three systematic reviews addressing regional priorities (1.5%). Furthermore, no systematic review focused on the Eastern Mediterranean region. Primary studies from the region had limited contribution to systematic reviews; 17 systematic reviews (8.5%) included primary studies conducted in the region. Conclusions There are still gaps in the production of systematic reviews addressing policymakers’ and stakeholders’ priorities in the Eastern Mediterranean region. Efforts should be directed towards better aligning systematic review production with policy needs and priorities. Study findings can inform the agendas of researchers, research institutions, and international funding agencies of priority areas where systematic reviews are required. PMID:25139256

A systematic review and meta-analysis of face-to-face communication of tailored health messages: implications for practice.

PubMed

Wanyonyi, Kristina L; Themessl-Huber, Markus; Humphris, Gerry; Freeman, Ruth

2011-12-01

To conduct a systematic review of the effect of face-to-face delivered tailored health messages on patient behavior and applications for practice. A systematic literature review and meta-analysis. Systematic searches of a number of electronic databases were conducted and criteria for selection of studies were specified. 6 experimental studies published between 2003 and 2009 were included. The studies were all randomized controlled trials to evaluate the effectiveness of a face-to-face tailored messaging intervention. There were variation in their research design and methods used to randomize. All participants were aged at least 18 years. All of the studies reported positive changes in participants' health behavior with varying degrees of effect size and duration. A meta-analysis of the available data also confirmed an overall positive effect of tailored messaging on participants' health behaviors. The systematic review and the meta-analysis demonstrate a significant and positive effective of face-to-face tailored messaging upon participants' health behaviors. Health practitioners should be encouraged to allot time in their work routines to discover their patients' psycho-social characteristics and felt needs in order that they can provide a tailored health message to enable the patient to adopt health-promoting regimes into their lifestyle. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Conducting systematic reviews of association (etiology): The Joanna Briggs Institute's approach.

PubMed

Moola, Sandeep; Munn, Zachary; Sears, Kim; Sfetcu, Raluca; Currie, Marian; Lisy, Karolina; Tufanaru, Catalin; Qureshi, Rubab; Mattis, Patrick; Mu, Peifan

2015-09-01

The systematic review of evidence is the research method which underpins the traditional approach to evidence-based healthcare. There is currently no uniform methodology for conducting a systematic review of association (etiology). This study outlines and describes the Joanna Briggs Institute's approach and guidance for synthesizing evidence related to association with a predominant focus on etiology and contributes to the emerging field of systematic review methodologies. It should be noted that questions of association typically address etiological or prognostic issues.The systematic review of studies to answer questions of etiology follows the same basic principles of systematic review of other types of data. An a priori protocol must inform the conduct of the systematic review, comprehensive searching must be performed and critical appraisal of retrieved studies must be carried out.The overarching objective of systematic reviews of etiology is to identify and synthesize the best available evidence on the factors of interest that are associated with a particular disease or outcome. The traditional PICO (population, interventions, comparators and outcomes) format for systematic reviews of effects does not align with questions relating to etiology. A systematic review of etiology should include the following aspects: population, exposure of interest (independent variable) and outcome (dependent variable).Studies of etiology are predominantly explanatory or predictive. The objective of reviews of explanatory or predictive studies is to contribute to, and improve our understanding of, the relationship of health-related events or outcomes by examining the association between variables. When interpreting possible associations between variables based on observational study data, caution must be exercised due to the likely presence of confounding variables or moderators that may impact on the results.As with all systematic reviews, there are various approaches to present the results, including a narrative, graphical or tabular summary, or meta-analysis. When meta-analysis is not possible, a set of alternative methods for synthesizing research is available. On the basis of the research question and objectives, narrative, tabular and/or visual approaches can be used for data synthesis. There are some special considerations when conducting meta-analysis for questions related to risk and correlation. These include, but are not limited to, causal inference.Systematic review and meta-analysis of studies related to etiology is an emerging methodology in the field of evidence synthesis. These reviews can provide useful information for healthcare professionals and policymakers on the burden of disease. The standardized Joanna Briggs Institute approach offers a rigorous and transparent method to conduct reviews of etiology.

Seeing the forests and the trees—innovative approaches to exploring heterogeneity in systematic reviews of complex interventions to enhance health system decision-making: a protocol

PubMed Central

2014-01-01

Background To improve quality of care and patient outcomes, health system decision-makers need to identify and implement effective interventions. An increasing number of systematic reviews document the effects of quality improvement programs to assist decision-makers in developing new initiatives. However, limitations in the reporting of primary studies and current meta-analysis methods (including approaches for exploring heterogeneity) reduce the utility of existing syntheses for health system decision-makers. This study will explore the role of innovative meta-analysis approaches and the added value of enriched and updated data for increasing the utility of systematic reviews of complex interventions. Methods/Design We will use the dataset from our recent systematic review of 142 randomized trials of diabetes quality improvement programs to evaluate novel approaches for exploring heterogeneity. These will include exploratory methods, such as multivariate meta-regression analyses and all-subsets combinatorial meta-analysis. We will then update our systematic review to include new trials and enrich the dataset by surveying authors of all included trials. In doing so, we will explore the impact of variables not, reported in previous publications, such as details of study context, on the effectiveness of the intervention. We will use innovative analytical methods on the enriched and updated dataset to identify key success factors in the implementation of quality improvement interventions for diabetes. Decision-makers will be involved throughout to help identify and prioritize variables to be explored and to aid in the interpretation and dissemination of results. Discussion This study will inform future systematic reviews of complex interventions and describe the value of enriching and updating data for exploring heterogeneity in meta-analysis. It will also result in an updated comprehensive systematic review of diabetes quality improvement interventions that will be useful to health system decision-makers in developing interventions to improve outcomes for people with diabetes. Systematic review registration PROSPERO registration no. CRD42013005165 PMID:25115289

Development and evaluation of 'briefing notes' as a novel knowledge translation tool to aid the implementation of sex/gender analysis in systematic reviews: a pilot study.

PubMed

Doull, Marion; Welch, Vivian; Puil, Lorri; Runnels, Vivien; Coen, Stephanie E; Shea, Beverley; O'Neill, Jennifer; Borkhoff, Cornelia; Tudiver, Sari; Boscoe, Madeline

2014-01-01

There is increasing recognition of sex/gender differences in health and the importance of identifying differential effects of interventions for men and women. Yet, to whom the research evidence does or does not apply, with regard to sex/gender, is often insufficiently answered. This is also true for systematic reviews which synthesize results of primary studies. A lack of analysis and reporting of evidence on sex/gender raises concerns about the applicability of systematic reviews. To bridge this gap, this pilot study aimed to translate knowledge about sex/gender analysis (SGA) into a user-friendly 'briefing note' format and evaluate its potential in aiding the implementation of SGA in systematic reviews. Our Sex/Gender Methods Group used an interactive process to translate knowledge about sex/gender into briefing notes, a concise communication tool used by policy and decision makers. The briefing notes were developed in collaboration with three Cochrane Collaboration review groups (HIV/AIDS, Hypertension, and Musculoskeletal) who were also the target knowledge users of the briefing notes. Briefing note development was informed by existing systematic review checklists, literature on sex/gender, in-person and virtual meetings, and consultation with topic experts. Finally, we held a workshop for potential users to evaluate the notes. Each briefing note provides tailored guidance on considering sex/gender to reviewers who are planning or conducting systematic reviews and includes the rationale for considering sex/gender, with examples specific to each review group's focus. Review authors found that the briefing notes provided welcome guidance on implementing SGA that was clear and concise, but also identified conceptual and implementation challenges. Sex/gender briefing notes are a promising knowledge translation tool. By encouraging sex/gender analysis and equity considerations in systematic reviews, the briefing notes can assist systematic reviewers in ensuring the applicability of research evidence, with the goal of improved health outcomes for diverse populations.

Cost-effectiveness of lung cancer screening and treatment methods: a systematic review of systematic reviews.

PubMed

Azar, Farbod Ebadifard; Azami-Aghdash, Saber; Pournaghi-Azar, Fatemeh; Mazdaki, Alireza; Rezapour, Aziz; Ebrahimi, Parvin; Yousefzadeh, Negar

2017-06-19

Due to extensive literature in the field of lung cancer and their heterogeneous results, the aim of this study was to systematically review of systematic reviews studies which reviewed the cost-effectiveness of various lung cancer screening and treatment methods. In this systematic review of systematic reviews study, required data were collected searching the following key words which selected from Mesh: "lung cancer", "lung oncology", "lung Carcinoma", "lung neoplasm", "lung tumors", "cost- effectiveness", "systematic review" and "Meta-analysis". The following databases were searched: PubMed, Cochrane Library electronic databases, Google Scholar, and Scopus. Two reviewers (RA and A-AS) evaluated the articles according to the checklist of "assessment of multiple systematic reviews" (AMSTAR) tool. Overall, information of 110 papers was discussed in eight systematic reviews. Authors focused on cost-effectiveness of lung cancer treatments in five systematic reviews. Targeted therapy options (bevacizumab, Erlotinib and Crizotinib) show an acceptable cost-effectiveness. Results of three studies failed to show cost-effectiveness of screening methods. None of the studies had used the meta-analysis method. The Quality of Health Economic Studies (QHES) tool and Drummond checklist were mostly used in assessing the quality of articles. Most perspective was related to the Payer (64 times) and the lowest was related to Social (11times). Most cases referred to Incremental analysis (82%) and also the lowest point of referral was related to Discounting (in 49% of the cases). The average quality score of included studies was calculated 9.2% from 11. Targeted therapy can be an option for the treatment of lung cancer. Evaluation of the cost-effectiveness of computerized tomographic colonography (CTC) in lung cancer screening is recommended. The perspective of the community should be more taken into consideration in studies of cost-effectiveness. Paying more attention to the topic of Discounting will be necessary in the studies.

Optimal strategies to consider when peer reviewing a systematic review and meta-analysis.

PubMed

Moher, David

2015-11-02

Systematic reviews are popular. A recent estimate indicates that 11 new systematic reviews are published daily. Nevertheless, evidence indicates that the quality of reporting of systematic reviews is not optimal. One likely reason is that the authors' reports have received inadequate peer review. There are now many different types of systematic reviews and peer reviewing them can be enhanced by using a reporting guideline to supplement whatever template the journal editors have asked you, as a peer reviewer, to use. Additionally, keeping up with the current literature, whether as a content expert or being aware of advances in systematic review methods is likely be make for a more comprehensive and effective peer review. Providing a brief summary of what the systematic review has reported is an important first step in the peer review process (and not performed frequently enough). At its core, it provides the authors with some sense of what the peer reviewer believes was performed (Methods) and found (Results). Importantly, it also provides clarity regarding any potential problems in the methods, including statistical approaches for meta-analysis, results, and interpretation of the systematic review, for which the peer reviewer can seek explanations from the authors; these clarifications are best presented as questions to the authors.

Analyse des erreurs et grammaire generative: La syntaxe de l'interrogation en francais (Error Analysis and Generative Grammar: The Syntax of Interrogation in French).

ERIC Educational Resources Information Center

Py, Bernard

A progress report is presented of a study which applies a system of generative grammar to error analysis. The objective of the study was to reconstruct the grammar of students' interlanguage, using a systematic analysis of errors. (Interlanguage refers to the linguistic competence of a student who possesses a relatively systematic body of rules,…

Acoustic Analysis of Voice in Singers: A Systematic Review

ERIC Educational Resources Information Center

Gunjawate, Dhanshree R.; Ravi, Rohit; Bellur, Rajashekhar

2018-01-01

Purpose: Singers are vocal athletes having specific demands from their voice and require special consideration during voice evaluation. Presently, there is a lack of standards for acoustic evaluation in them. The aim of the present study was to systematically review the available literature on the acoustic analysis of voice in singers. Method: A…

School-Based Mentoring for Adolescents: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Wood, Sarah; Mayo-Wilson, Evan

2012-01-01

Objectives: To evaluate the impact of school-based mentoring for adolescents (11-18 years) on academic performance, attendance, attitudes, behavior, and self-esteem. Method: A systematic review and meta-analysis. The authors searched 12 databases from 1980 to 2011. Eight studies with 6,072 participants were included, 6 were included in…

Brain-Derived Neurotrophic Factor Levels in Autism: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Saghazadeh, Amene; Rezaei, Nima

2017-01-01

Brain-derived neurotrophic factor (BDNF) plays an important role in activity-dependent synaptic plasticity. Altered blood BDNF levels have been frequently identified in people with autism spectrum disorders (ASD). There are however wide discrepancies in the evidence. Therefore, we performed the present systematic review and meta-analysis aimed at…

Systematic Review and Meta-Analysis of the "Skills for Social and Academic Success" ("SASS") Program

ERIC Educational Resources Information Center

Mychailyszyn, Matthew P.

2017-01-01

The purpose of this systematic review and meta-analysis was to synthesize the available research on the "Skills for Social and Academic Success" ("SASS") program, a school-based cognitive/behavioural intervention for adolescents with social anxiety disorder. A search of online databases, combined with reference list examination…

Treatment for School Refusal among Children and Adolescents: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Maynard, Brandy R.; Heyne, David; Brendel, Kristen Esposito; Bulanda, Jeffery J.; Thompson, Aaron M.; Pigott, Terri D.

2018-01-01

Objective: School refusal is a psychosocial problem associated with adverse short- and long-term consequences for children and adolescents. The authors conducted a systematic review and meta-analysis to examine the effects of psychosocial treatments for children and adolescents with school refusal. Method: A comprehensive search process was used…

Digital Games, Design, and Learning: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Clark, Douglas B.; Tanner-Smith, Emily E.; Killingsworth, Stephen S.

2016-01-01

In this meta-analysis, we systematically reviewed research on digital games and learning for K-16 students. We synthesized comparisons of game versus nongame conditions (i.e., media comparisons) and comparisons of augmented games versus standard game designs (i.e., value-added comparisons). We used random-effects meta-regression models with robust…

Neutrophil-to-lymphocyte ratio as a prognostic indicator in head and neck cancer: A systematic review and meta-analysis.

PubMed

Tham, Tristan; Bardash, Yonatan; Herman, Saori Wendy; Costantino, Peter David

2018-05-14

The purposes of this systematic review and meta-analysis were to investigate the relationship between the neutrophil-to-lymphocyte ratio (NLR) and prognosis in head and neck cancer. A systematic review and meta-analysis were done to investigate the role of NLR in overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), and progression-free survival (PFS). For qualitative analysis, 33 cohorts with over 10 072 patients were included. For quantitative analysis, 15 studies were included with 5562 patients. The pooled data demonstrated that an elevated NLR significantly predicted poorer OS and DSS. An elevated pretreatment NLR is a prognostic marker for head and neck cancer. It represents a simple and easily obtained marker that could be used to stratify groups of high-risk patients who might benefit from adjuvant therapy. © 2018 Wiley Periodicals, Inc.

UNDERSTANDING SYSTEMATIC MEASUREMENT ERROR IN THERMAL-OPTICAL ANALYSIS FOR PM BLACK CARBON USING RESPONSE SURFACES AND SURFACE CONFIDENCE INTERVALS

EPA Science Inventory

Results from a NIST-EPA Interagency Agreement on Understanding Systematic Measurement Error in Thermal-Optical Analysis for PM Black Carbon Using Response Surfaces and Surface Confidence Intervals will be presented at the American Association for Aerosol Research (AAAR) 24th Annu...

Vitamin D and Depression: A Systematic Review and Meta-Analysis Comparing Studies with and without Biological Flaws

PubMed Central

Spedding, Simon

2014-01-01

Efficacy of Vitamin D supplements in depression is controversial, awaiting further literature analysis. Biological flaws in primary studies is a possible reason meta-analyses of Vitamin D have failed to demonstrate efficacy. This systematic review and meta-analysis of Vitamin D and depression compared studies with and without biological flaws. The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The literature search was undertaken through four databases for randomized controlled trials (RCTs). Studies were critically appraised for methodological quality and biological flaws, in relation to the hypothesis and study design. Meta-analyses were performed for studies according to the presence of biological flaws. The 15 RCTs identified provide a more comprehensive evidence-base than previous systematic reviews; methodological quality of studies was generally good and methodology was diverse. A meta-analysis of all studies without flaws demonstrated a statistically significant improvement in depression with Vitamin D supplements (+0.78 CI +0.24, +1.27). Studies with biological flaws were mainly inconclusive, with the meta-analysis demonstrating a statistically significant worsening in depression by taking Vitamin D supplements (−1.1 CI −0.7, −1.5). Vitamin D supplementation (≥800 I.U. daily) was somewhat favorable in the management of depression in studies that demonstrate a change in vitamin levels, and the effect size was comparable to that of anti-depressant medication. PMID:24732019

Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation.

PubMed

Shamseer, Larissa; Moher, David; Clarke, Mike; Ghersi, Davina; Liberati, Alessandro; Petticrew, Mark; Shekelle, Paul; Stewart, Lesley A

2015-01-02

Protocols of systematic reviews and meta-analyses allow for planning and documentation of review methods, act as a guard against arbitrary decision making during review conduct, enable readers to assess for the presence of selective reporting against completed reviews, and, when made publicly available, reduce duplication of efforts and potentially prompt collaboration. Evidence documenting the existence of selective reporting and excessive duplication of reviews on the same or similar topics is accumulating and many calls have been made in support of the documentation and public availability of review protocols. Several efforts have emerged in recent years to rectify these problems, including development of an international register for prospective reviews (PROSPERO) and launch of the first open access journal dedicated to the exclusive publication of systematic review products, including protocols (BioMed Central's Systematic Reviews). Furthering these efforts and building on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines, an international group of experts has created a guideline to improve the transparency, accuracy, completeness, and frequency of documented systematic review and meta-analysis protocols--PRISMA-P (for protocols) 2015. The PRISMA-P checklist contains 17 items considered to be essential and minimum components of a systematic review or meta-analysis protocol.This PRISMA-P 2015 Explanation and Elaboration paper provides readers with a full understanding of and evidence about the necessity of each item as well as a model example from an existing published protocol. This paper should be read together with the PRISMA-P 2015 statement. Systematic review authors and assessors are strongly encouraged to make use of PRISMA-P when drafting and appraising review protocols. © BMJ Publishing Group Ltd 2014.

Does the endometrial gene expression of fertile women vary within and between cycles?

PubMed

Evans, Gloria E; Phillipson, Gregory T M; Sykes, Peter H; McNoe, Les A; Print, Cristin G; Evans, John J

2018-01-23

Does gene expression of putative endometrial implantation markers vary in expression between menstrual cycles? In fertile women the expression of certain genes exhibits a pattern of stable regulation.which is not affected even when sampled twice in one cycle. Successful implantation occurs in a minority of IVF embryo transfers. In contrast to knowledge regarding the ovulatory process, there is a sparse understanding of endometrial genes critical to implantation. This lack of knowledge hinders progress in this field. Endometrial pipelle samples were collected based on blood endocrinological markers at 2 and 7 days post initial LH surge. Five samples were collected over four cycles where the interval between collections ranged from sequential months to three years. Six fertile women attending an IVF clinic for male factor infertility, had samples collected. Global gene expression profiles were obtained from laser-microdissected, endometrial glands and stroma. Nineteen potential proliferation, cytokine and adhesion markers based on previous validated reports were studied. There was a significant modification between LH+2 and LH+7 of expression for 23 genes-11 in 8 in glands and stroma, 4 in stroma only and 3 in glands only suggesting stable, controlled regulation. Nevertheless, genes exhibited individual characteristics, e.g MKI67 exhibited lower expression at LH+7 than LH+2 and CCL4 higher, whereas TRO expressed limited difference in both cell types. Stability between cycles was demonstrated for gene expression at both LH+2-more than 60% of genes had <25% variation and at LH+7-60% had <30% variation. Further, effects of prior collection of an LH+2 sample on gene expression at LH+7 were not detected. The range of mRNA expression suggested that a clinical/diagnostic sample at LH+2 and LH+7 is likely to be a better index of endometrial function than a single sample. The possibility of redundancy suggests a panel would be more informative than a single marker. Raw and normalized microarray data have been deposited with the EMBL's European Genome-Phenome Archive for collaborative analysis, reference ega-box-815 (Lappalainen I, Almeida-King J, Kumanduri V, Senf A, Spalding JD, Ur-Rehman S, Saunders G, Kandasamy J, Caccamo M, Leinonen R et al. The European Genome-phenome Archive of human data consented for biomedical research. Nat Genet 2015;47:692-695.) [https://www.ebi.ac.uk/ega/home]. This type of research has difficulties of recruitment of fertile women for multiple blood testing and repeat endometrial biopsies. Therefore, these data had decreased statistical power due to the overall participant numbers. However, the inclusion of four cycles for each participant permitted the aim of obtaining information on intercycle and intracycle variability to be achieved. Our results support the feasibility of a clinical means of identification of a functional receptive endometrium. The robustness of data from individual women suggests that samples from one cycle can generally be applied to subsequent cycles. Funding was granted from the Tertiary Education Commission of New Zealand, Contract I.D.:UOOX06007. There are no competing interests. © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Analysis of Arterial Blood Gas Report in Chronic Kidney Diseases - Comparison between Bedside and Multistep Systematic Method.

PubMed

Ghatak, Ishita; Dhat, Vaishali; Tilak, Mona A; Roy, Indranath

2016-08-01

Acid Base Disorders (ABDs) are commonly encountered in critically ill Chronic Kidney Disease (CKD) patients. Timely and correct analysis of Arterial Blood Gases (ABG) is critical for the diagnosis, treatment and prediction of outcome of the patients. The aim was to explore type and prevalence of ABDs in 31 critically ill CKD patients from a tertiary care hospital in Maharashtra, to compare two methods of analysis- bedside and systematic approaches and to clinically correlate the nature of ABDs in these patients. The initial ABG reports of 31 consecutive CKD patients were analysed by two methods. Medica Easy stat analyser was the equipment for analysis with Principle of potentiometry and ion selective electrode for pH and pCO2 and amperometry for pO2. Serum albumin was also measured by Bromocresol green dye binding method using liquixx albumin kit in Erba XL 300 autoanalyser. Chi-square test was used for statistical analysis using Epi Info version 3.5.4 and SPSS 14.0 softwares. The systematic method showed a significantly higher prevalence of mixed disorders (50%) compared to bedside method (12.9%). Most prevalent disorder by bedside method was metabolic acidosis in 15 cases (48.39%). By the systematic method, 3 reports were invalid. As a single category, most prevalent type was both simple respiratory alkalosis and mixed metabolic acidosis with respiratory alkalosis- 6 of 31 cases in each type (19.36% each). As a whole, metabolic acidosis (including both High Anion Gap Metabolic Acidosis or HAGMA and Non Anion Gap Metabolic Acidosis or NAGMA with 4 in each type) was most prevalent- 8 of 31(25.8%). Systematic approach was more effective in diagnosing mixed acid base disorders. By systematic method the findings of analysis in most cases could be correlated with the clinical condition and provisional diagnosis. Thus interpretation of ABDs by using stepwise approach could be useful to the clinicians in early diagnosis and management of the patients.

Comparative Analysis of Dentinal Erosion after Passive Ultrasonic Irrigation versus Irrigation with Reciprocating Activation: An Environmental Scanning Electron Study.

PubMed

Simezo, Ana Paula; da Silveira Bueno, Carlos Eduardo; Cunha, Rodrigo Sanches; Pelegrine, Rina Andrea; Rocha, Daniel Guimarães Pedro; de Martin, Alexandre Sigrist; Kato, Augusto Shoji

2017-01-01

The aim of this study was to assess ex vivo the erosive effects of passive ultrasonic irrigation versus irrigation with reciprocating activation on the dentinal surface of the root canal at 3 predetermined levels using environmental scanning electron microscopy. Ten roots of mandibular premolars were prepared using the ProTaper Universal system (Dentsply Maillefer, Ballaigues, Switzerland). The specimens were embedded in flasks cleaved longitudinally, and indentations were made 3.0, 6.0, and 9.0 mm from the apex. The specimens in the control group (n = 10) were cleaned in an ultrasonic bath containing 2.5% sodium hypochlorite and 17% EDTA and then dried. Then, environmental scanning electron microscopic images were obtained at magnification × 800. The specimens were then reassembled in their flasks, and the NaOCl and EDTA solutions were activated according to the conditions established for the experimental groups (ie, the passive ultrasonic irrigation group [n = 5] and the EasyClean (Easy Equipamentos Odontológicos, Belo Horizonte, MG, Brazil) group, irrigation with reciprocating activation with the EasyClean instrument [n = 5]). The specimens of both experimental groups were analyzed in the same manner as in the control group. Analysis of the dentinal surface topography was conducted using the 3D Roughness Reconstruction program (Phenom-World BV, Eindhoven, the Netherlands) as a means for assessing erosion. The data were evaluated by means of the Kruskal-Wallis, Student-Newman-Keuls, and Mann-Whitney tests. In the EasyClean group, the degree of dentinal erosion at 3.0 mm was significantly higher than at 9.0 mm. In the other comparisons, there was no statistically significant difference (P < .05). The final irrigation techniques tested were equivalent in relation to the degree of erosion caused to the dentinal surface. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Learning by Doing--Teaching Systematic Review Methods in 8 Weeks

ERIC Educational Resources Information Center

Li, Tianjing; Saldanha, Ian J.; Vedula, S. Swaroop; Yu, Tsung; Rosman, Lori; Twose, Claire; Goodman, Steven N.; Dickersin, Kay

2014-01-01

Objective: The objective of this paper is to describe the course "Systematic Reviews and Meta-analysis" at the Johns Hopkins Bloomberg School of Public Health. Methods: A distinct feature of our course is a group project in which students, assigned to multi-disciplinary groups, conduct a systematic review. In-class sessions comprise…

Methodological Reflections on the Use of Systematic Reviews in Early Childhood Research

ERIC Educational Resources Information Center

Ang, Lynn

2018-01-01

This article sets out to look critically at the use of systematic reviews in the cross-disciplinary field of early childhood and international development. Systematic reviews--a specialist methodology involving the secondary analysis of existing knowledge on a particular topic--is prevalently used to address complex questions in social and…

Systematic reviews do not adequately report or address missing outcome data in their analyses: a methodological survey.

PubMed

Kahale, Lara A; Diab, Batoul; Brignardello-Petersen, Romina; Agarwal, Arnav; Mustafa, Reem A; Kwong, Joey; Neumann, Ignacio; Li, Ling; Lopes, Luciane Cruz; Briel, Matthias; Busse, Jason W; Iorio, Alfonso; Vandvik, Per Olav; Alexander, Paul Elias; Guyatt, Gordon; Akl, Elie A

2018-07-01

To describe how systematic review authors report and address categories of participants with potential missing outcome data of trial participants. Methodological survey of systematic reviews reporting a group-level meta-analysis. We included a random sample of 50 Cochrane and 50 non-Cochrane systematic reviews. Of these, 25 reported in their methods section a plan to consider at least one of the 10 categories of missing outcome data; 42 reported in their results, data for at least one category of missing data. The most reported category in the methods and results sections was "unexplained loss to follow-up" (n = 34 in methods section and n = 6 in the results section). Only 19 reported a method to handle missing data in their primary analyses, which was most often complete case analysis. Few reviews (n = 9) reported in the methods section conducting sensitivity analysis to judge risk of bias associated with missing outcome data at the level of the meta-analysis; and only five of them presented the results of these analyses in the results section. Most systematic reviews do not explicitly report sufficient information on categories of trial participants with potential missing outcome data or address missing data in their primary analyses. Copyright © 2018 Elsevier Inc. All rights reserved.

SYFSA: A Framework for Systematic Yet Flexible Systems Analysis

PubMed Central

Johnson, Todd R.; Markowitz, Eliz; Bernstam, Elmer V.; Herskovic, Jorge R.; Thimbleby, Harold

2013-01-01

Although technological or organizational systems that enforce systematic procedures and best practices can lead to improvements in quality, these systems must also be designed to allow users to adapt to the inherent uncertainty, complexity, and variations in healthcare. We present a framework, called Systematic Yet Flexible Systems Analysis (SYFSA) that supports the design and analysis of Systematic Yet Flexible (SYF) systems (whether organizational or technical) by formally considering the tradeoffs between systematicity and flexibility. SYFSA is based on analyzing a task using three related problem spaces: the idealized space, the natural space, and the system space. The idealized space represents the best practice—how the task is to be accomplished under ideal conditions. The natural space captures the task actions and constraints on how the task is currently done. The system space specifies how the task is done in a redesigned system, including how it may deviate from the idealized space, and how the system supports or enforces task constraints. The goal of the framework is to support the design of systems that allow graceful degradation from the idealized space to the natural space. We demonstrate the application of SYFSA for the analysis of a simplified central line insertion task. We also describe several information-theoretic measures of flexibility that can be used to compare alternative designs, and to measure how efficiently a system supports a given task, the relative cognitive workload, and learnability. PMID:23727053

School-Based Education Programs for the Prevention of Child Sexual Abuse: A Cochrane Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Walsh, Kerryann; Zwi, Karen; Woolfenden, Susan; Shlonsky, Aron

2018-01-01

Objective: To assess evidence of the effectiveness of school-based education programs for the prevention of child sexual abuse (CSA). The programs deliver information about CSA and strategies to help children avoid it and encourage help seeking. Methods: Systematic review including meta-analysis of randomized controlled trials (RCTs), cluster…

Stepping Stones Triple P-Positive Parenting Program for Children with Disability: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Tellegen, Cassandra L.; Sanders, Matthew R.

2013-01-01

This systematic review and meta-analysis evaluated the treatment effects of a behavioral family intervention, Stepping Stones Triple P (SSTP) for parents of children with disabilities. SSTP is a system of five intervention levels of increasing intensity and narrowing population reach. Twelve studies, including a total of 659 families, met…

A Systematic Review and Meta-Analysis of Predictors of Expressive-Language Outcomes among Late Talkers

ERIC Educational Resources Information Center

Fisher, Evelyn L.

2017-01-01

Purpose: The purpose of this study was to explore the literature on predictors of outcomes among late talkers using systematic review and meta-analysis methods. We sought to answer the question: What factors predict preschool-age expressive-language outcomes among late-talking toddlers? Method: We entered carefully selected search terms into the…

Academic Interventions for Elementary and Middle School Students with Low Socioeconomic Status: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Dietrichson, Jens; Bøg, Martin; Filges, Trine; Klint Jørgensen, Anne-Marie

2017-01-01

Socioeconomic status is a major predictor of educational achievement. This systematic review and meta-analysis seeks to identify effective academic interventions for elementary and middle school students with low socioeconomic status. Included studies have used a treatment-control group design, were performed in OECD and EU countries, and measured…

A Systematic Review and Meta-Analysis of Indicated Interventions to Increase School Attendance

ERIC Educational Resources Information Center

Maynard, Brandy R.; Tyson-McCrea, Katherine; Pigott, Therese; Kelly, Michael

2011-01-01

The main objective of this systematic review and meta-analysis was to examine the effects of intervention programs on school attendance behaviors of elementary and secondary school students to inform policy and practice. The specific questions guiding this study were: (1) Do indicated programs with a goal of increasing student attendance affect…

Psychological Treatments for Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Lackner, Jeffrey M.; Mesmer, Christina; Morley, Stephen; Dowzer, Clare; Hamilton, Simon

2004-01-01

This study conducted a systematic review to assess the quality of existing literature on psychological treatments for irritable bowel syndrome and to quantify the evidence for their efficacy. Three independent reviewers (2 from England, 1 from the United States) coded the quality of 32 studies, 17 of which provided data suitable for meta-analysis.…

Anxiety Disorders in Williams Syndrome Contrasted with Intellectual Disability and the General Population: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Royston, R.; Howlin, P.; Waite, J.; Oliver, C.

2017-01-01

Individuals with specific genetic syndromes associated with intellectual disability (ID), such as Williams syndrome (WS), are at increased risk for developing anxiety disorders. A systematic literature review identified sixteen WS papers that could generate pooled prevalence estimates of anxiety disorders for WS. A meta-analysis compared these…

The reporting quality of meta-analysis results of systematic review abstracts in periodontology and implant dentistry is suboptimal.

PubMed

Polychronopoulou, Argy

2014-12-01

Assessment of the quality of reporting in abstracts of systematic reviews with meta-analyses in periodontology and implant dentistry. Faggion CM Jr., Liu J, Huda F, Atieh M. J Periodontal Res 2014; 49(2):137-42. Argy Polychronopoulou, DDS, MS, ScM, ScD PURPOSE/QUESTION: What is the reporting quality of meta-analysis results of abstracts of systematic reviews in periodontology and implant dentistry journals? The authors received no funding for this study Meta-epidemiological study Level 3: Other evidence Not applicable. Copyright © 2014 Elsevier Inc. All rights reserved.

Factors influencing citations to systematic reviews in skin diseases: a cross-sectional study through Web of Sciences and Scopus.

PubMed

Manriquez, Juan; Cataldo, Karina; Harz, Isidora

2015-01-01

Disseminating information derived from systematic reviews is a fundamental step for translating evidence into practice. To determine which features of dermatological SR are associated with systematic review dissemination, using citation rates as an indicator. Dermatological systematic reviews published between 2008 and 2012 were obtained from Scopus, the ISI Web of Sciences and the Cochrane Skin Group. Bibliometric data of every systematic review were collected and analyzed. A total of 320 systematic reviews were analyzed. Univariable analysis showed that the journal impact factor, number of authors, and total references cited were positively associated with the number of citations. There was a significant difference in the median number of citations with regard to the corresponding author's country, type of skin disease, type of funding, and presence of international collaboration. Cochrane reviews were significantly associated with a lower number of citations. Multivariable analysis found that the number of authors, number of references cited and the corresponding author from United Kingdom were independently correlated with many citations. Cochrane systematic reviews tended to be independently associated with a lower number of citations. Citation number to systematic reviews may be improving by increasing the number of authors, especially collaborative authors, and the number of cited references. The reasons for the association of Cochrane SRs with fewer citations should be addressed in future studies.

Factors influencing citations to systematic reviews in skin diseases: a cross-sectional study through Web of Sciences and Scopus*

PubMed Central

Manriquez, Juan; Cataldo, Karina; Harz, Isidora

2015-01-01

BACKGROUND Disseminating information derived from systematic reviews is a fundamental step for translating evidence into practice. OBJECTIVE To determine which features of dermatological SR are associated with systematic review dissemination, using citation rates as an indicator. METHODS Dermatological systematic reviews published between 2008 and 2012 were obtained from Scopus, the ISI Web of Sciences and the Cochrane Skin Group. Bibliometric data of every systematic review were collected and analyzed. RESULTS A total of 320 systematic reviews were analyzed. Univariable analysis showed that the journal impact factor, number of authors, and total references cited were positively associated with the number of citations. There was a significant difference in the median number of citations with regard to the corresponding author's country, type of skin disease, type of funding, and presence of international collaboration. Cochrane reviews were significantly associated with a lower number of citations. Multivariable analysis found that the number of authors, number of references cited and the corresponding author from United Kingdom were independently correlated with many citations. Cochrane systematic reviews tended to be independently associated with a lower number of citations. CONCLUSIONS Citation number to systematic reviews may be improving by increasing the number of authors, especially collaborative authors, and the number of cited references. The reasons for the association of Cochrane SRs with fewer citations should be addressed in future studies. PMID:26560209

A novel approach for data integration and disease subtyping

PubMed Central

Tagett, Rebecca; Diaz, Diana

2017-01-01

Advances in high-throughput technologies allow for measurements of many types of omics data, yet the meaningful integration of several different data types remains a significant challenge. Another important and difficult problem is the discovery of molecular disease subtypes characterized by relevant clinical differences, such as survival. Here we present a novel approach, called perturbation clustering for data integration and disease subtyping (PINS), which is able to address both challenges. The framework has been validated on thousands of cancer samples, using gene expression, DNA methylation, noncoding microRNA, and copy number variation data available from the Gene Expression Omnibus, the Broad Institute, The Cancer Genome Atlas (TCGA), and the European Genome-Phenome Archive. This simultaneous subtyping approach accurately identifies known cancer subtypes and novel subgroups of patients with significantly different survival profiles. The results were obtained from genome-scale molecular data without any other type of prior knowledge. The approach is sufficiently general to replace existing unsupervised clustering approaches outside the scope of bio-medical research, with the additional ability to integrate multiple types of data. PMID:29066617

The digital revolution in phenotyping

PubMed Central

Oellrich, Anika; Collier, Nigel; Groza, Tudor; Rebholz-Schuhmann, Dietrich; Shah, Nigam; Bodenreider, Olivier; Boland, Mary Regina; Georgiev, Ivo; Liu, Hongfang; Livingston, Kevin; Luna, Augustin; Mallon, Ann-Marie; Manda, Prashanti; Robinson, Peter N.; Rustici, Gabriella; Simon, Michelle; Wang, Liqin; Winnenburg, Rainer; Dumontier, Michel

2016-01-01

Phenotypes have gained increased notoriety in the clinical and biological domain owing to their application in numerous areas such as the discovery of disease genes and drug targets, phylogenetics and pharmacogenomics. Phenotypes, defined as observable characteristics of organisms, can be seen as one of the bridges that lead to a translation of experimental findings into clinical applications and thereby support ‘bench to bedside’ efforts. However, to build this translational bridge, a common and universal understanding of phenotypes is required that goes beyond domain-specific definitions. To achieve this ambitious goal, a digital revolution is ongoing that enables the encoding of data in computer-readable formats and the data storage in specialized repositories, ready for integration, enabling translational research. While phenome research is an ongoing endeavor, the true potential hidden in the currently available data still needs to be unlocked, offering exciting opportunities for the forthcoming years. Here, we provide insights into the state-of-the-art in digital phenotyping, by means of representing, acquiring and analyzing phenotype data. In addition, we provide visions of this field for future research work that could enable better applications of phenotype data. PMID:26420780

Mining the Human Phenome using Semantic Web Technologies: A Case Study for Type 2 Diabetes

PubMed Central

Pathak, Jyotishman; Kiefer, Richard C.; Bielinski, Suzette J.; Chute, Christopher G.

2012-01-01

The ability to conduct genome-wide association studies (GWAS) has enabled new exploration of how genetic variations contribute to health and disease etiology. However, historically GWAS have been limited by inadequate sample size due to associated costs for genotyping and phenotyping of study subjects. This has prompted several academic medical centers to form “biobanks” where biospecimens linked to personal health information, typically in electronic health records (EHRs), are collected and stored on large number of subjects. This provides tremendous opportunities to discover novel genotype-phenotype associations and foster hypothesis generation. In this work, we study how emerging Semantic Web technologies can be applied in conjunction with clinical and genotype data stored at the Mayo Clinic Biobank to mine the phenotype data for genetic associations. In particular, we demonstrate the role of using Resource Description Framework (RDF) for representing EHR diagnoses and procedure data, and enable federated querying via standardized Web protocols to identify subjects genotyped with Type 2 Diabetes for discovering gene-disease associations. Our study highlights the potential of Web-scale data federation techniques to execute complex queries. PMID:23304343

Interview: the National Institute of Neurological Diseases and Stroke/American Epilepsy Society benchmarks and research priorities for epilepsy research.

PubMed

Lowenstein, Daniel H

2011-10-01

Daniel H Lowenstein, MD, is the Robert B and Ellinor Aird Professor and Vice-Chairman of Neurology, Director of the Epilepsy Center, and Director of Physician-Scientist Education and Training at the University of California, San Francisco (UCSF). He received his BA in Mathematics from the University of Colorado and MD from Harvard Medical School. He completed his neurology residency training at UCSF. Dr Lowenstein is a clinician-scientist who has studied both basic science and clinical aspects of epilepsy. In recent years, he has been an organizer of a large-scale, international effort to study the complex genetics of epilepsy, known as the Epilepsy Phenome/Genome Project. He has been actively involved in advancing the cause of epilepsy at the national and international level. Dr Lowenstein served as President of the American Epilepsy Society from 2003 to 2004 and the National Institute of Neurological Diseases and Stroke (NINDS) Advisory Council from 2000 to 2004, and has overseen the development of the NINDS Epilepsy Research Benchmarks since their inception in 2000.

Redefining meaningful age groups in the context of disease.

PubMed

Geifman, Nophar; Cohen, Raphael; Rubin, Eitan

2013-12-01

Age is an important factor when considering phenotypic changes in health and disease. Currently, the use of age information in medicine is somewhat simplistic, with ages commonly being grouped into a small number of crude ranges reflecting the major stages of development and aging, such as childhood or adolescence. Here, we investigate the possibility of redefining age groups using the recently developed Age-Phenome Knowledge-base (APK) that holds over 35,000 literature-derived entries describing relationships between age and phenotype. Clustering of APK data suggests 13 new, partially overlapping, age groups. The diseases that define these groups suggest that the proposed divisions are biologically meaningful. We further show that the number of different age ranges that should be considered depends on the type of disease being evaluated. This finding was further strengthened by similar results obtained from clinical blood measurement data. The grouping of diseases that share a similar pattern of disease-related reports directly mirrors, in some cases, medical knowledge of disease-age relationships. In other cases, our results may be used to generate new and reasonable hypotheses regarding links between diseases.

Mining the human phenome using semantic web technologies: a case study for Type 2 Diabetes.

PubMed

Pathak, Jyotishman; Kiefer, Richard C; Bielinski, Suzette J; Chute, Christopher G

2012-01-01

The ability to conduct genome-wide association studies (GWAS) has enabled new exploration of how genetic variations contribute to health and disease etiology. However, historically GWAS have been limited by inadequate sample size due to associated costs for genotyping and phenotyping of study subjects. This has prompted several academic medical centers to form "biobanks" where biospecimens linked to personal health information, typically in electronic health records (EHRs), are collected and stored on large number of subjects. This provides tremendous opportunities to discover novel genotype-phenotype associations and foster hypothesis generation. In this work, we study how emerging Semantic Web technologies can be applied in conjunction with clinical and genotype data stored at the Mayo Clinic Biobank to mine the phenotype data for genetic associations. In particular, we demonstrate the role of using Resource Description Framework (RDF) for representing EHR diagnoses and procedure data, and enable federated querying via standardized Web protocols to identify subjects genotyped with Type 2 Diabetes for discovering gene-disease associations. Our study highlights the potential of Web-scale data federation techniques to execute complex queries.

Cost effectiveness analysis of screening for sight threatening diabetic eye disease

PubMed Central

James, Marilyn; Turner, David A; Broadbent, Deborah M; Vora, Jiten; Harding, Simon P

2000-01-01

Objective To measure the cost effectiveness of systematic photographic screening for sight threatening diabetic eye disease compared with existing practice. Design Cost effectiveness analysis Setting Liverpool. Subjects A target population of 5000 diabetic patients invited for screening. Main outcome measures Cost effectiveness (cost per true positive) of systematic and opportunistic programmes; incremental cost effectiveness of replacing opportunistic with systematic screening. Results Baseline prevalence of sight threatening eye disease was 14.1%. The cost effectiveness of the systematic programme was £209 (sensitivity 89%, specificity 86%, compliance 80%, annual cost £104 996) and of the opportunistic programme was £289 (combined sensitivity 63%, specificity 92%, compliance 78%, annual cost £99 981). The incremental cost effectiveness of completely replacing the opportunistic programme was £32. Absolute values of cost effectiveness were highly sensitive to varying prevalence, sensitivity and specificity, compliance, and programme size. Conclusion Replacing existing programmes with systematic screening for diabetic eye disease is justified. PMID:10856062

Interpretive analysis of 85 systematic reviews suggests that narrative syntheses and meta‐analyses are incommensurate in argumentation

PubMed Central

O'Mara‐Eves, A.; Thomas, J.; Brunton, G.; Caird, J.; Petticrew, M.

2016-01-01

Using Toulmin's argumentation theory, we analysed the texts of systematic reviews in the area of workplace health promotion to explore differences in the modes of reasoning embedded in reports of narrative synthesis as compared with reports of meta‐analysis. We used framework synthesis, grounded theory and cross‐case analysis methods to analyse 85 systematic reviews addressing intervention effectiveness in workplace health promotion. Two core categories, or ‘modes of reasoning’, emerged to frame the contrast between narrative synthesis and meta‐analysis: practical–configurational reasoning in narrative synthesis (‘what is going on here? What picture emerges?’) and inferential–predictive reasoning in meta‐analysis (‘does it work, and how well? Will it work again?’). Modes of reasoning examined quality and consistency of the included evidence differently. Meta‐analyses clearly distinguished between warrant and claim, whereas narrative syntheses often presented joint warrant–claims. Narrative syntheses and meta‐analyses represent different modes of reasoning. Systematic reviewers are likely to be addressing research questions in different ways with each method. It is important to consider narrative synthesis in its own right as a method and to develop specific quality criteria and understandings of how it is carried out, not merely as a complement to, or second‐best option for, meta‐analysis. © 2016 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd. PMID:27860329

Applicability and feasibility of systematic review for performing evidence-based risk assessment in food and feed safety.

PubMed

Aiassa, E; Higgins, J P T; Frampton, G K; Greiner, M; Afonso, A; Amzal, B; Deeks, J; Dorne, J-L; Glanville, J; Lövei, G L; Nienstedt, K; O'connor, A M; Pullin, A S; Rajić, A; Verloo, D

2015-01-01

Food and feed safety risk assessment uses multi-parameter models to evaluate the likelihood of adverse events associated with exposure to hazards in human health, plant health, animal health, animal welfare, and the environment. Systematic review and meta-analysis are established methods for answering questions in health care, and can be implemented to minimize biases in food and feed safety risk assessment. However, no methodological frameworks exist for refining risk assessment multi-parameter models into questions suitable for systematic review, and use of meta-analysis to estimate all parameters required by a risk model may not be always feasible. This paper describes novel approaches for determining question suitability and for prioritizing questions for systematic review in this area. Risk assessment questions that aim to estimate a parameter are likely to be suitable for systematic review. Such questions can be structured by their "key elements" [e.g., for intervention questions, the population(s), intervention(s), comparator(s), and outcome(s)]. Prioritization of questions to be addressed by systematic review relies on the likely impact and related uncertainty of individual parameters in the risk model. This approach to planning and prioritizing systematic review seems to have useful implications for producing evidence-based food and feed safety risk assessment.

[Quality appraisal of systematic reviews or meta-analysis on traditional Chinese medicine published in Chinese journals].

PubMed

Liu, Jian-ping; Xia, Yun

2007-04-01

To critically assess the quality of literature about systematic review or meta-analysis on traditional Chinese medicine (TCM) published in Chinese journals. Electronic searches in CNKI, VIP and Wanfang data-base were conducted to retrieve the systematic reviews or meta-analysis reports on TCM, including herbal medicine, needling, acupuncture and moxibustion, as well as integrative medicine, they were identified and extracted according to the 18 items of QUOROM (quality of reporting of meta-analyses) Statement and relative information. The appraisal was made taking the indexes mainly including objectives, source of data, methods of data extraction, quality assessment of the included studies, measurement data synthesis, etc. Eighty-two systematic reviews were identified, except 6 reviews were excluded for repeatedly published or didn't comply with the enrolled criterion, 76 reviews concerning 51 kinds of diseases were enrolled for appraisal. Among them, 70 reviews evaluated the efficacy of TCM, mainly on Chinese herbs and 9 on acupuncture and moxibustion. In majority of the reviews, randomised controlled trials were included and the data resources were described, but in 26 reviews only the Chinese databases were searched and the description about data extraction and analysis method were too simple; and 70% of reviews assessed the quality of the included studies; none used flow chart to express the process of selection, inclusion and exclusion of studies. Few reviews or Meta-analysis reports reached the international standard and there is insufficient description of methodology for conducting systematic reviews, so it is hardly to be repeated. The authors suggested that advanced methodological training is necessary for reviewers.

Corticosteroids vs corticosteroids plus antiviral agents in the treatment of Bell palsy: a systematic review and meta-analysis.

PubMed

Goudakos, John K; Markou, Konstantinos D

2009-06-01

To review systematically and meta-analyze the results of all randomized controlled trials (RCTs) for the treatment of patients with Bell palsy with corticosteroids vs corticosteroids plus antiviral agents. A MEDLINE, EMBASE, Cochrane Library, and CENTRAL database search, followed by extensive hand-searching for the identification of relevant studies. No time and language limitations were applied. Prospective RCTs on the treatment of patients with Bell palsy. Odds ratios (ORs), 95% confidence intervals (CIs), and tests for heterogeneity were reported. Five studies were eventually identified and systematically reviewed. Meta-analysis was performed for 4 studies. Regarding the complete recovery rate of facial nerve paralysis 3 months after initiation of therapy, the current systematic review and meta-analysis suggests that the addition of an antiviral agent does not provide any benefit (OR, 1.03 [95% CI, 0.74-1.42]; P = .88). The same conclusion emerged at posterior (fourth, sixth, and ninth) months of assessment. Subgroup analysis, conducted on the basis of time point of therapy initiation, type of antiviral agent, and blindness of assessments did not change the results obtained. The occurrence rate of adverse effects attributable to therapy choice was not significantly different between patients receiving corticosteroids and those following combined treatment. The present systematic review and meta-analysis, based on the currently available evidence, suggests that the addition of an antiviral agent to corticosteroids for the treatment of Bell palsy is not associated with an increase in the complete recovery rate of the facial motor function.

[Systematic umbilical cord blood analysis at birth: feasibility and reliability in a French labour ward].

PubMed

Ernst, D; Clerc, J; Decullier, E; Gavanier, G; Dupuis, O

2012-10-01

At birth, evaluation of neonatal well-being is crucial. It is though important to perform umbilical cord blood gas analysis, and then to analyze the samples. We wanted to establish the feasibility and reliability of systematic umbilical cord blood sampling in a French labour ward. Study of systematic umbilical cord blood gas analysis was realized retrospectively from 1000 consecutive deliveries. We first established the feasibility of the samples. Feasibility was defined by the ratio of complete cord acid-base data on the number of deliveries from alive newborns. Afterwards, we established the reliability on the remaining cord samples. Reliability was the ratio of samples that fulfilled quality criteria defined by Westgate et al. and revised by Kro et al., on the number of complete samples from alive newborns. At last, we looked for factors that would influence these results. The systematic umbilical cord blood sample feasibility reached 91.6%, and the reliability reached 80.7%. About the delivery mode, 38.6% of emergency caesarians (IC 95% [30.8-46.3]; P<0.0001) led to non-valid samples, when only 11.3% of programmed caesarians (IC 95% [4.3-18.2]; P<0.0001) led to non-valid samples. Umbilical cord blood analysis were significantly less validated during emergency caesarians. Realization of systematic cord blood gas analysis was followed by 8.4% of incomplete samples, and by 19.3% that were uninterpretable. Training sessions should be organized to improve the feasibility and reliability, especially during emergency caesarians. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Development and Evaluation of ‘Briefing Notes’ as a Novel Knowledge Translation Tool to Aid the Implementation of Sex/Gender Analysis in Systematic Reviews: A Pilot Study

PubMed Central

Doull, Marion; Welch, Vivian; Puil, Lorri; Runnels, Vivien; Coen, Stephanie E.; Shea, Beverley; O’Neill, Jennifer; Borkhoff, Cornelia; Tudiver, Sari; Boscoe, Madeline

2014-01-01

Background There is increasing recognition of sex/gender differences in health and the importance of identifying differential effects of interventions for men and women. Yet, to whom the research evidence does or does not apply, with regard to sex/gender, is often insufficiently answered. This is also true for systematic reviews which synthesize results of primary studies. A lack of analysis and reporting of evidence on sex/gender raises concerns about the applicability of systematic reviews. To bridge this gap, this pilot study aimed to translate knowledge about sex/gender analysis (SGA) into a user-friendly ‘briefing note’ format and evaluate its potential in aiding the implementation of SGA in systematic reviews. Methods Our Sex/Gender Methods Group used an interactive process to translate knowledge about sex/gender into briefing notes, a concise communication tool used by policy and decision makers. The briefing notes were developed in collaboration with three Cochrane Collaboration review groups (HIV/AIDS, Hypertension, and Musculoskeletal) who were also the target knowledge users of the briefing notes. Briefing note development was informed by existing systematic review checklists, literature on sex/gender, in-person and virtual meetings, and consultation with topic experts. Finally, we held a workshop for potential users to evaluate the notes. Results Each briefing note provides tailored guidance on considering sex/gender to reviewers who are planning or conducting systematic reviews and includes the rationale for considering sex/gender, with examples specific to each review group’s focus. Review authors found that the briefing notes provided welcome guidance on implementing SGA that was clear and concise, but also identified conceptual and implementation challenges. Conclusions Sex/gender briefing notes are a promising knowledge translation tool. By encouraging sex/gender analysis and equity considerations in systematic reviews, the briefing notes can assist systematic reviewers in ensuring the applicability of research evidence, with the goal of improved health outcomes for diverse populations. PMID:25372876

A systematic review and meta-analysis of music therapy for the older adults with depression.

PubMed

Zhao, K; Bai, Z G; Bo, A; Chi, I

2016-11-01

To determine the efficacy of music therapy in the management of depression in the elderly. We conducted a systematic review and meta-analysis of randomized controlled trials. Change in depressive symptoms was measured with various scales. Standardized mean differences were calculated for each therapy-control contrast. A comprehensive search yielded 2,692 citations; 19 articles met inclusion criteria. Meta-analysis suggests that music therapy plus standard treatment has statistical significance in reducing depressive symptoms among older adults (standardized mean differences = 1.02; 95% CI = 0.87, 1.17). This systematic review and meta-analysis suggests that music therapy has an effect on reducing depressive symptoms to some extent. However, high-quality trials evaluating the effects of music therapy on depression are required. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Effect of Preventive Interventions in Mentally Ill Parents on the Mental Health of the Offspring: Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Siegenthaler, Eliane; Munder, Thomas; Egger, Matthias

2012-01-01

Objective: Mental illness in parents affects the mental health of their children. A systematic review and a meta-analysis of the effectiveness of interventions to prevent mental disorders or psychological symptoms in the offspring were performed. Method: The Cochrane, MEDLINE, EMBASE, and PsycINFO databases were searched for randomized controlled…

School-Based Sleep Education Programs for Short Sleep Duration in Adolescents: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Chung, Ka-Fai; Chan, Man-Sum; Lam, Ying-Yin; Lai, Cindy Sin-Yee; Yeung, Wing-Fai

2017-01-01

Background: Insufficient sleep among students is a major school health problem. School-based sleep education programs tailored to reach large number of students may be one of the solutions. A systematic review and meta-analysis was conducted to summarize the programs' effectiveness and current status. Methods: Electronic databases were searched up…

How Will DSM-5 Affect Autism Diagnosis? A Systematic Literature Review and Meta-Analysis

ERIC Educational Resources Information Center

Kulage, Kristine M.; Smaldone, Arlene M.; Cohn, Elizabeth G.

2014-01-01

We conducted a systematic review and meta-analysis to determine the effect of changes to the Diagnostic and Statistical Manual (DSM)-5 on autism spectrum disorder (ASD) and explore policy implications. We identified 418 studies; 14 met inclusion criteria. Studies consistently reported decreases in ASD diagnosis (range 7.3-68.4%) using DSM-5…

Are School Nurses an Overlooked Resource in Reducing Childhood Obesity? A Systematic Review and Meta-analysis

ERIC Educational Resources Information Center

Schroeder, Krista; Travers, Jasmine; Smaldone, Arlene

2016-01-01

Background: Schools are a key setting for childhood obesity interventions, yet nurses are not often included in delivering these interventions. The objective of this systematic review and meta-analysis was to examine school-based interventions involving nurses in a role beyond anthropometric measurement for effect on change in body measures.…

Maternal Diabetes and the Risk of Autism Spectrum Disorders in the Offspring: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Xu, Guifeng; Jing, Jin; Bowers, Katherine; Liu, Buyun; Bao, Wei

2014-01-01

We performed a systematic literature search regarding maternal diabetes before and during pregnancy and the risk of autism spectrum disorders (ASD) in the offspring. Of the 178 potentially relevant articles, 12 articles including three cohort studies and nine case-control studies were included in the meta-analysis. Both the meta-analyses of cohort…

Relation between Alice Software and Programming Learning: A Systematic Review of the Literature and Meta-Analysis

ERIC Educational Resources Information Center

Costa, Joana M.; Miranda, Guilhermina L.

2017-01-01

This paper presents the results of a systematic review of the literature, including a meta-analysis, about the effectiveness of the use of Alice software in programming learning when compared to the use of a conventional programming language. Our research included studies published between the years 2000 and 2014 in the main databases. We gathered…

Effect of exercise on cognitive function in chronic disease patients: a meta-analysis and systematic review of randomized controlled trials.

PubMed

Cai, Hong; Li, Guichen; Hua, Shanshan; Liu, Yufei; Chen, Li

2017-01-01

The purpose of this study was to conduct a meta-analysis and systematic review to assess the effect of exercise on cognitive function in people with chronic diseases. PubMed, Web of Science, Embase, the Cochrane Library, CINAHL, PsycINFO, and three Chinese databases were electronically searched for papers that were published until September 2016. This meta-analysis and systematic review included randomized controlled trials that evaluated the effect of exercise on cognitive function compared with control group for people with chronic diseases. Totally, 35 studies met the inclusion criteria, with 3,113 participants. The main analysis revealed a positive overall random effect of exercise intervention on cognitive function in patients with chronic diseases. The secondary analysis revealed that aerobic exercise interventions and aerobic included exercise interventions had a positive effect on cognition in patients with chronic diseases. The intervention offering low frequency had a positive effect on cognitive function in patients with chronic diseases. Finally, we found that interventions offered at both low exercise intensity and moderate exercise intensity had a positive effect on cognitive function in patients with chronic diseases. The secondary analysis also revealed that exercise interventions were beneficial in Alzheimer's disease patients when grouped by disease type. This meta-analysis and systematic review suggests that exercise interventions positively influence cognitive function in patients with chronic diseases. Beneficial effect was independent of the type of disease, type of exercise, frequency, and the intensity of the exercise intervention.

Meteoritic Sulfur Isotopic Analysis

NASA Technical Reports Server (NTRS)

Thiemens, Mark H.

1996-01-01

Funds were requested to continue our program in meteoritic sulfur isotopic analysis. We have recently detected a potential nucleosynthetic sulfur isotopic anomaly. We will search for potential carriers. The documentation of bulk systematics and the possible relation to nebular chemistry and oxygen isotopes will be explored. Analytical techniques for delta(sup 33), delta(sup 34)S, delta(sup 36)S isotopic analysis were improved. Analysis of sub milligram samples is now possible. A possible relation between sulfur isotopes and oxygen was detected, with similar group systematics noted, particularly in the case of aubrites, ureilites and entstatite chondrites. A possible nucleosynthetic excess S-33 has been noted in bulk ureilites and an oldhamite separate from Norton County. High energy proton (approximately 1 GeV) bombardments of iron foils were done to experimentally determine S-33, S-36 spallogenic yields for quantitation of isotopic measurements in iron meteorites. Techniques for measurement of mineral separates were perfected and an analysis program initiated. The systematic behavior of bulk sulfur isotopes will continue to be explored.

Association Between the Estrogen Receptor Beta (ESR2) Rs1256120 Single Nucleotide Polymorphism and Adolescent Idiopathic Scoliosis: A Systematic Review and Meta-Analysis.

PubMed

Zhao, Linlu; Roffey, Darren M; Chen, Suzan

2017-06-01

A systematic review and meta-analysis. The aim of this study was to assess and synthesize the current evidence on the association between the rs1256120 single nucleotide polymorphism (SNP) of the estrogen receptor beta gene (ESR2) and adolescent idiopathic scoliosis (AIS). Hormonal disturbance has been postulated as a potential etiological factor in the development of AIS. As estrogen receptors are important mediators of estrogen response, mutations in these genes, including rs1256120 of ESR2, have been chosen as susceptibility candidates for AIS predisposition. The association of rs1256120 with AIS has been investigated in several recent studies, but showed conflicting evidence. We conducted a systematic review to evaluate the strength of this body of evidence and quantitative synthesis to examine sources of heterogeneity. This study conformed to PRISMA guidelines. Using a sensitive search strategy, PubMed (MEDLINE), EMBASE, and HuGE Literature Finder databases were searched to identify relevant studies for inclusion in the systematic review and meta-analysis. Risk of bias was assessed using a modified Newcastle-Ottawa Scale. The inverse variance model was used to calculate summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the allelic (C vs. T) and genotypic comparisons. Planned subgroup and sensitivity analyses were performed. Three studies were included for systematic review and meta-analysis (n = 1264 AIS cases and n=1020 controls). A null relationship was found between rs1256120 and AIS (allelic OR = 1.20, 95% CI: 0.81-1.78, P = 0.36, I = 84.9%), with the first reported association likely to be false-positive and contributing substantially to heterogeneity. Findings from the systematic review and meta-analysis suggest that rs1256120 of ESR2 is unlikely to be a predisposing or disease-modifying genetic risk factor for AIS. 2.

SystEmatic review and meta-aNAlysis of infanT and young child feeding Practices (ENAT-P) in Ethiopia: protocol

PubMed Central

Islam, Md. Atiqul; Sharew, Nigussie Tadesse; Birhanu, Mulugeta Molla; Tegegne, Balewgizie Sileshi

2017-01-01

Introduction Infant and young child feeding (IYCF) is the cornerstone of infant and child survival, healthy growth and development, healthy future generations and national development. In spite of the importance of optimal nutrition in low- and middle-income countries, there has been no review conducted in Ethiopia. Thus, the aim of this systematic review and meta-analysis is to estimate the national coverage and identify the associated factors of IYCF practices in Ethiopia. Methods PubMed, Scopus, EMBASE, CINHAL, EBSCO, Web of Science and WHO Global Health Library databases will be searched for all available publications from 1 January 2000 to 30 September 2017. All published studies on the timely initiation of breast feeding, exclusive breast feeding and timely initiation of complementary feeding practice in Ethiopia will be screened, selected and reviewed. Bibliographies of identified articles and grey literature will be hand-searched as well. Heterogeneity of studies will be quantified using Higgins’s method where I2 statistic >80% indicates substantial heterogeneity. Funnel plots and Egger’s regression test will be used to assess potential publication bias. The Newcastle–Ottawa Scale (NOS) will be used to assess the quality of evidence and risk of bias. Meta-analysis and meta-regression will be carried out to estimate the pooled national prevalence rate and an OR of each associated factor of IYCF practices. Narrative synthesis will be performed if meta-analysis is not feasible due to the substantial heterogeneity of studies. Ethics and dissemination Ethical clearance is not required for this study because primary data will not be collected. The results of this systematic review and meta-analysis will be published in a peer-reviewed journal and presented at an (inter)national research symposium. Systematic review registration This systematic review and meta-analysis has been registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42017056768. PMID:28775196

Does consideration and assessment of effects on health equity affect the conclusions of systematic reviews? A methodology study.

PubMed

Welch, Vivian; Petticrew, Mark; Ueffing, Erin; Benkhalti Jandu, Maria; Brand, Kevin; Dhaliwal, Bharbhoor; Kristjansson, Elizabeth; Smylie, Janet; Wells, George Anthony; Tugwell, Peter

2012-01-01

Tackling health inequities both within and between countries remains high on the agenda of international organizations including the World Health Organization and local, regional and national governments. Systematic reviews can be a useful tool to assess effects on equity in health status because they include studies conducted in a variety of settings and populations. This study aims to describe the extent to which the impacts of health interventions on equity in health status are considered in systematic reviews, describe methods used, and assess the implications of their equity related findings for policy, practice and research. We conducted a methodology study of equity assessment in systematic reviews. Two independent reviewers extracted information on the reporting and analysis of impacts of health interventions on equity in health status in a group of 300 systematic reviews collected from all systematic reviews indexed in one month of MEDLINE, using a pre-tested data collection form. Any differences in data extraction were resolved by discussion. Of the 300 systematic reviews, 224 assessed the effectiveness of interventions on health outcomes. Of these 224 reviews, 29 systematic reviews assessed effects on equity in health status using subgroup analysis or targeted analyses of vulnerable populations. Of these, seven conducted subgroup analyses related to health equity which were reported in insufficient detail to judge their credibility. Of these 29 reviews, 18 described implications for policy and practice based on assessment of effects on health equity. The quality and completeness of reporting should be enhanced as a priority, because without this policymakers and practitioners will continue lack the evidence base they need to inform decision-making about health inequity. Furthermore, there is a need to develop methods to systematically consider impacts on equity in health status that is currently lacking in systematic reviews.

Continued Analysis of the NIST Neutron Lifetime Measurement Using Ultracold Neutrons

NASA Astrophysics Data System (ADS)

Huffer, Craig; Huffman, P. R.; Schelhammer, K. W.; Dewey, M. S.; Huber, M. G.; Hughes, P. P.; Mumm, H. P.; Thompson, A. K.; Coakley, K.; Yue, A. T.; O'Shaughnessy, C. M.; Yang, L.

2013-10-01

The neutron lifetime is an important parameter for constraining the Standard Model and providing input for Big Bang Nucleosynthesis. The current disagreement in the most recent generation of lifetime experiments suggests unknown or underestimated systematics and motivates the need for alternative measurement methods as well as additional investigations into potential systematics. Our measurement was performed using magnetically trapped Ultracold Neutrons in a 3.1 T Ioffe type trap configuration. The decay rate of the neutron population is recorded in real time by monitoring visible light resulting from beta decay. Data collected in late 2010 and early 2011 is being analyzed and systematic effects are being investigated. An overview of our current work on the analysis, Monte Carlo simulations, and systematic effects will be provided. This work was supported by the NSF and NIST.

Effects of Spaced Retrieval Training on Semantic Memory in Alzheimer's Disease: A Systematic Review

ERIC Educational Resources Information Center

Oren, Shiri; Willerton, Charlene; Small, Jeff

2014-01-01

Purpose: This article reports on a systematic review and meta-analysis of the effects of spaced retrieval training (SRT) on semantic memory in people with Alzheimer's disease (AD) or related disorder. Method: An initial systematic database search identified 454 potential studies. After screening and de-duplication, 35 studies that used SRT…

Voice, Articulation, and Prosody Contribute to Listener Perceptions of Speaker Gender: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Leung, Yeptain; Oates, Jennifer; Chan, Siew Pang

2018-01-01

Purpose: The aim of this study was to provide a systematic review of the aspects of verbal communication contributing to listener perceptions of speaker gender with a view to providing clinicians with guidance for the selection of the training goals when working with transsexual individuals. Method: Preferred reporting items for systematic review…

Systematic reviews, systematic error and the acquisition of clinical knowledge

PubMed Central

2010-01-01

Background Since its inception, evidence-based medicine and its application through systematic reviews, has been widely accepted. However, it has also been strongly criticised and resisted by some academic groups and clinicians. One of the main criticisms of evidence-based medicine is that it appears to claim to have unique access to absolute scientific truth and thus devalues and replaces other types of knowledge sources. Discussion The various types of clinical knowledge sources are categorised on the basis of Kant's categories of knowledge acquisition, as being either 'analytic' or 'synthetic'. It is shown that these categories do not act in opposition but rather, depend upon each other. The unity of analysis and synthesis in knowledge acquisition is demonstrated during the process of systematic reviewing of clinical trials. Systematic reviews constitute comprehensive synthesis of clinical knowledge but depend upon plausible, analytical hypothesis development for the trials reviewed. The dangers of systematic error regarding the internal validity of acquired knowledge are highlighted on the basis of empirical evidence. It has been shown that the systematic review process reduces systematic error, thus ensuring high internal validity. It is argued that this process does not exclude other types of knowledge sources. Instead, amongst these other types it functions as an integrated element during the acquisition of clinical knowledge. Conclusions The acquisition of clinical knowledge is based on interaction between analysis and synthesis. Systematic reviews provide the highest form of synthetic knowledge acquisition in terms of achieving internal validity of results. In that capacity it informs the analytic knowledge of the clinician but does not replace it. PMID:20537172

Effectiveness of virtual reality training for balance and gait rehabilitation in people with multiple sclerosis: a systematic review and meta-analysis.

PubMed

Casuso-Holgado, María Jesús; Martín-Valero, Rocío; Carazo, Ana F; Medrano-Sánchez, Esther M; Cortés-Vega, M Dolores; Montero-Bancalero, Francisco José

2018-04-01

To evaluate the evidence for the use of virtual reality to treat balance and gait impairments in multiple sclerosis rehabilitation. Systematic review and meta-analysis of randomized controlled trials and quasi-randomized clinical trials. An electronic search was conducted using the following databases: MEDLINE (PubMed), Physiotherapy Evidence Database (PEDro), Cochrane Database of Systematic Reviews (CDSR) and (CINHAL). A quality assessment was performed using the PEDro scale. The data were pooled and a meta-analysis was completed. This systematic review was conducted in accordance with the (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) PRISMA guideline statement. It was registered in the PROSPERO database (CRD42016049360). A total of 11 studies were included. The data were pooled, allowing meta-analysis of seven outcomes of interest. A total of 466 participants clinically diagnosed with multiple sclerosis were analysed. Results showed that virtual reality balance training is more effective than no intervention for postural control improvement (standard mean difference (SMD) = -0.64; 95% confidence interval (CI) = -1.05, -0.24; P = 0.002). However, significant overall effect was not showed when compared with conventional training (SMD = -0.04; 95% CI = -0.70, 0.62; P = 0.90). Inconclusive results were also observed for gait rehabilitation. Virtual reality training could be considered at least as effective as conventional training and more effective than no intervention to treat balance and gait impairments in multiple sclerosis rehabilitation.

Recent meta-analyses neglect previous systematic reviews and meta-analyses about the same topic: a systematic examination.

PubMed

Helfer, Bartosz; Prosser, Aaron; Samara, Myrto T; Geddes, John R; Cipriani, Andrea; Davis, John M; Mavridis, Dimitris; Salanti, Georgia; Leucht, Stefan

2015-04-14

As the number of systematic reviews is growing rapidly, we systematically investigate whether meta-analyses published in leading medical journals present an outline of available evidence by referring to previous meta-analyses and systematic reviews. We searched PubMed for recent meta-analyses of pharmacological treatments published in high impact factor journals. Previous systematic reviews and meta-analyses were identified with electronic searches of keywords and by searching reference sections. We analyzed the number of meta-analyses and systematic reviews that were cited, described and discussed in each recent meta-analysis. Moreover, we investigated publication characteristics that potentially influence the referencing practices. We identified 52 recent meta-analyses and 242 previous meta-analyses on the same topics. Of these, 66% of identified previous meta-analyses were cited, 36% described, and only 20% discussed by recent meta-analyses. The probability of citing a previous meta-analysis was positively associated with its publication in a journal with a higher impact factor (odds ratio, 1.49; 95% confidence interval, 1.06 to 2.10) and more recent publication year (odds ratio, 1.19; 95% confidence interval 1.03 to 1.37). Additionally, the probability of a previous study being described by the recent meta-analysis was inversely associated with the concordance of results (odds ratio, 0.38; 95% confidence interval, 0.17 to 0.88), and the probability of being discussed was increased for previous studies that employed meta-analytic methods (odds ratio, 32.36; 95% confidence interval, 2.00 to 522.85). Meta-analyses on pharmacological treatments do not consistently refer to and discuss findings of previous meta-analyses on the same topic. Such neglect can lead to research waste and be confusing for readers. Journals should make the discussion of related meta-analyses mandatory.

Do health technology assessments comply with QUOROM diagram guidance? An empirical study.

PubMed

Hind, Daniel; Booth, Andrew

2007-11-20

The Quality of Reporting of Meta-analyses (QUOROM) statement provides guidance for improving the quality of reporting of systematic reviews and meta-analyses. To make the process of study selection transparent it recommends "a flow diagram providing information about the number of RCTs identified, included, and excluded and the reasons for excluding them". We undertook an empirical study to identify the extent of compliance in the UK Health Technology Assessment (HTA) programme. We searched Medline to retrieve all systematic reviews of therapeutic interventions in the HTA monograph series published from 2001 to 2005. Two researchers recorded whether each study contained a meta-analysis of controlled trials, whether a QUOROM flow diagram was presented and, if so, whether it expressed the relationship between the number of citations and the number of studies. We used Cohen's kappa to test inter-rater reliability. 87 systematic reviews were retrieved. There was good and excellent inter-rater reliability for, respectively, whether a review contained a meta-analysis and whether each diagram contained a citation-to-study relationship. 49% of systematic reviews used a study selection flow diagram. When only systematic reviews containing a meta-analysis were analysed, compliance was only 32%. Only 20 studies (23% of all systematic reviews; 43% of those having a study selection diagram) had a diagram which expressed the relationship between citations and studies. Compliance with the recommendations of the QUOROM statement is not universal in systematic reviews or meta-analyses. Flow diagrams make the conduct of study selection transparent only if the relationship between citations and studies is clearly expressed. Reviewers should understand what they are counting: citations, papers, studies and trials are fundamentally different concepts which should not be confused in a diagram.

Aquaculture genomics, genetics and breeding in the United States: current status, challenges, and priorities for future research.

PubMed

Abdelrahman, Hisham; ElHady, Mohamed; Alcivar-Warren, Acacia; Allen, Standish; Al-Tobasei, Rafet; Bao, Lisui; Beck, Ben; Blackburn, Harvey; Bosworth, Brian; Buchanan, John; Chappell, Jesse; Daniels, William; Dong, Sheng; Dunham, Rex; Durland, Evan; Elaswad, Ahmed; Gomez-Chiarri, Marta; Gosh, Kamal; Guo, Ximing; Hackett, Perry; Hanson, Terry; Hedgecock, Dennis; Howard, Tiffany; Holland, Leigh; Jackson, Molly; Jin, Yulin; Khalil, Karim; Kocher, Thomas; Leeds, Tim; Li, Ning; Lindsey, Lauren; Liu, Shikai; Liu, Zhanjiang; Martin, Kyle; Novriadi, Romi; Odin, Ramjie; Palti, Yniv; Peatman, Eric; Proestou, Dina; Qin, Guyu; Reading, Benjamin; Rexroad, Caird; Roberts, Steven; Salem, Mohamed; Severin, Andrew; Shi, Huitong; Shoemaker, Craig; Stiles, Sheila; Tan, Suxu; Tang, Kathy F J; Thongda, Wilawan; Tiersch, Terrence; Tomasso, Joseph; Prabowo, Wendy Tri; Vallejo, Roger; van der Steen, Hein; Vo, Khoi; Waldbieser, Geoff; Wang, Hanping; Wang, Xiaozhu; Xiang, Jianhai; Yang, Yujia; Yant, Roger; Yuan, Zihao; Zeng, Qifan; Zhou, Tao

2017-02-20

Advancing the production efficiency and profitability of aquaculture is dependent upon the ability to utilize a diverse array of genetic resources. The ultimate goals of aquaculture genomics, genetics and breeding research are to enhance aquaculture production efficiency, sustainability, product quality, and profitability in support of the commercial sector and for the benefit of consumers. In order to achieve these goals, it is important to understand the genomic structure and organization of aquaculture species, and their genomic and phenomic variations, as well as the genetic basis of traits and their interrelationships. In addition, it is also important to understand the mechanisms of regulation and evolutionary conservation at the levels of genome, transcriptome, proteome, epigenome, and systems biology. With genomic information and information between the genomes and phenomes, technologies for marker/causal mutation-assisted selection, genome selection, and genome editing can be developed for applications in aquaculture. A set of genomic tools and resources must be made available including reference genome sequences and their annotations (including coding and non-coding regulatory elements), genome-wide polymorphic markers, efficient genotyping platforms, high-density and high-resolution linkage maps, and transcriptome resources including non-coding transcripts. Genomic and genetic control of important performance and production traits, such as disease resistance, feed conversion efficiency, growth rate, processing yield, behaviour, reproductive characteristics, and tolerance to environmental stressors like low dissolved oxygen, high or low water temperature and salinity, must be understood. QTL need to be identified, validated across strains, lines and populations, and their mechanisms of control understood. Causal gene(s) need to be identified. Genetic and epigenetic regulation of important aquaculture traits need to be determined, and technologies for marker-assisted selection, causal gene/mutation-assisted selection, genome selection, and genome editing using CRISPR and other technologies must be developed, demonstrated with applicability, and application to aquaculture industries.Major progress has been made in aquaculture genomics for dozens of fish and shellfish species including the development of genetic linkage maps, physical maps, microarrays, single nucleotide polymorphism (SNP) arrays, transcriptome databases and various stages of genome reference sequences. This paper provides a general review of the current status, challenges and future research needs of aquaculture genomics, genetics, and breeding, with a focus on major aquaculture species in the United States: catfish, rainbow trout, Atlantic salmon, tilapia, striped bass, oysters, and shrimp. While the overall research priorities and the practical goals are similar across various aquaculture species, the current status in each species should dictate the next priority areas within the species. This paper is an output of the USDA Workshop for Aquaculture Genomics, Genetics, and Breeding held in late March 2016 in Auburn, Alabama, with participants from all parts of the United States.

[Achene morphology cluster analysis of Taraxacum F. H. Wigg. from northeast China and molecule systematics evidence determined by SRAP].

PubMed

Li, Hai-juan; Zhao, Xin; Jia, Qing-fei; Li, Tian-lai; Ning, Wei

2012-08-01

The achenes morphological and micro-morphological characteristics of six species of genus Taraxacum from northeastern China as well as SRAP cluster analysis were observed for their classification evidences. The achenes were observed by microscope and EPMA. Cluster analysis was given on the basis of the size, shape, cone proportion, color and surface sculpture of achenes. The Taraxacum inter-species achene shape characteristic difference is obvious, particularly spinulose distribution and size, achene color and achene size; with the Taraxacum plant achene shape the cluster method T. antungense Kitag. and the T. urbanum Kitag. should combine for the identical kind; the achene morphology cluster analysis and the SRAP tagged molecule systematics's cluster result retrieves in the table with "the Chinese flora". The class group to divide the result is consistent. Taraxacum plant achene shape characteristic stable conservative, may carry on the inter-species division and the sibship analysis according to the achene shape characteristic combination difference; the achene morphology cluster analysis as well as the SRAP tagged molecule systematics confirmation support dandelion classification result of "the Chinese flora".

GenomeFingerprinter: the genome fingerprint and the universal genome fingerprint analysis for systematic comparative genomics.

PubMed

Ai, Yuncan; Ai, Hannan; Meng, Fanmei; Zhao, Lei

2013-01-01

No attention has been paid on comparing a set of genome sequences crossing genetic components and biological categories with far divergence over large size range. We define it as the systematic comparative genomics and aim to develop the methodology. First, we create a method, GenomeFingerprinter, to unambiguously produce a set of three-dimensional coordinates from a sequence, followed by one three-dimensional plot and six two-dimensional trajectory projections, to illustrate the genome fingerprint of a given genome sequence. Second, we develop a set of concepts and tools, and thereby establish a method called the universal genome fingerprint analysis (UGFA). Particularly, we define the total genetic component configuration (TGCC) (including chromosome, plasmid, and phage) for describing a strain as a systematic unit, the universal genome fingerprint map (UGFM) of TGCC for differentiating strains as a universal system, and the systematic comparative genomics (SCG) for comparing a set of genomes crossing genetic components and biological categories. Third, we construct a method of quantitative analysis to compare two genomes by using the outcome dataset of genome fingerprint analysis. Specifically, we define the geometric center and its geometric mean for a given genome fingerprint map, followed by the Euclidean distance, the differentiate rate, and the weighted differentiate rate to quantitatively describe the difference between two genomes of comparison. Moreover, we demonstrate the applications through case studies on various genome sequences, giving tremendous insights into the critical issues in microbial genomics and taxonomy. We have created a method, GenomeFingerprinter, for rapidly computing, geometrically visualizing, intuitively comparing a set of genomes at genome fingerprint level, and hence established a method called the universal genome fingerprint analysis, as well as developed a method of quantitative analysis of the outcome dataset. These have set up the methodology of systematic comparative genomics based on the genome fingerprint analysis.

Longitudinal analysis of reporting and quality of systematic reviews in high-impact surgical journals.

PubMed

Chapman, S J; Drake, T M; Bolton, W S; Barnard, J; Bhangu, A

2017-02-01

The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Statement aims to optimize the reporting of systematic reviews. The performance of the PRISMA Statement in improving the reporting and quality of surgical systematic reviews remains unclear. Systematic reviews published in five high-impact surgical journals between 2007 and 2015 were identified from online archives. Manuscripts blinded to journal, publication year and authorship were assessed according to 27 reporting criteria described by the PRISMA Statement and scored using a validated quality appraisal tool (AMSTAR, Assessing the Methodological Quality of Systematic Reviews). Comparisons were made between studies published before (2007-2009) and after (2011-2015) its introduction. The relationship between reporting and study quality was measured using Spearman's rank test. Of 281 eligible manuscripts, 80 were published before the PRISMA Statement and 201 afterwards. Most manuscripts (208) included a meta-analysis, with the remainder comprising a systematic review only. There was no meaningful change in median compliance with the PRISMA Statement (19 (i.q.r. 16-21) of 27 items before versus 19 (17-22) of 27 after introduction of PRISMA) despite achieving statistical significance (P = 0·042). Better reporting compliance was associated with higher methodological quality (r s  = 0·70, P < 0·001). The PRISMA Statement has had minimal impact on the reporting of surgical systematic reviews. Better compliance was associated with higher-quality methodology. © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

Using the Autism-Spectrum Quotient to Measure Autistic Traits in Anorexia Nervosa: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Westwood, Heather; Eisler, Ivan; Mandy, William; Leppanen, Jenni; Treasure, Janet; Tchanturia, Kate

2016-01-01

Interest in the link between Autism Spectrum Disorder (ASD) and Anorexia Nervosa (AN) has led to estimates of the prevalence of autistic traits in AN. This systematic review and meta-analysis assessed the use of the Autism-Spectrum Quotient (AQ) or abbreviated version (AQ-10) to examine whether patients with AN have elevated levels of autistic…

Gender and Age Differences in the Core Triad of Impairments in Autism Spectrum Disorders: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Wijngaarden-Cremers, Patricia J. M.; van Eeten, Evelien; Groen, Wouter B.; Van Deurzen, Patricia A.; Oosterling, Iris J.; Van der Gaag, Rutger Jan

2014-01-01

Autism is an extensively studied disorder in which the gender disparity in prevalence has received much attention. In contrast, only a few studies examine gender differences in symptomatology. This systematic review and meta-analysis of 22 peer reviewed original publications examines gender differences in the core triad of impairments in autism.…

Marigold (Calendula officinalis L.): an evidence-based systematic review by the Natural Standard Research Collaboration.

PubMed

Basch, Ethan; Bent, Steve; Foppa, Ivo; Haskmi, Sadaf; Kroll, David; Mele, Michelle; Szapary, Philippe; Ulbricht, Catherine; Vora, Mamta; Yong, Sophanna

2006-01-01

An evidence-based systematic review including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology and dosing.

An evidence-based systematic review of saffron (Crocus sativus) by the Natural Standard Research Collaboration.

PubMed

Ulbricht, Catherine; Conquer, Julie; Costa, Dawn; Hollands, Whitney; Iannuzzi, Carmen; Isaac, Richard; Jordan, Joseph K; Ledesma, Natalie; Ostroff, Cathy; Serrano, Jill M Grimes; Shaffer, Michael D; Varghese, Minney

2011-03-01

An evidence-based systematic review including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

Evidence-based systematic review of saw palmetto by the Natural Standard Research Collaboration.

PubMed

Ulbricht, Catherine; Basch, Ethan; Bent, Steve; Boon, Heather; Corrado, Michelle; Foppa, Ivo; Hashmi, Sadaf; Hammerness, Paul; Kingsbury, Eileen; Smith, Michael; Szapary, Philippe; Vora, Mamta; Weissner, Wendy

2006-01-01

Here presented is an evidence-based systematic review including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

Use of regularized principal component analysis to model anatomical changes during head and neck radiation therapy for treatment adaptation and response assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chetvertkov, Mikhail A., E-mail: chetvertkov@wayne

2016-10-15

Purpose: To develop standard (SPCA) and regularized (RPCA) principal component analysis models of anatomical changes from daily cone beam CTs (CBCTs) of head and neck (H&N) patients and assess their potential use in adaptive radiation therapy, and for extracting quantitative information for treatment response assessment. Methods: Planning CT images of ten H&N patients were artificially deformed to create “digital phantom” images, which modeled systematic anatomical changes during radiation therapy. Artificial deformations closely mirrored patients’ actual deformations and were interpolated to generate 35 synthetic CBCTs, representing evolving anatomy over 35 fractions. Deformation vector fields (DVFs) were acquired between pCT and syntheticmore » CBCTs (i.e., digital phantoms) and between pCT and clinical CBCTs. Patient-specific SPCA and RPCA models were built from these synthetic and clinical DVF sets. EigenDVFs (EDVFs) having the largest eigenvalues were hypothesized to capture the major anatomical deformations during treatment. Results: Principal component analysis (PCA) models achieve variable results, depending on the size and location of anatomical change. Random changes prevent or degrade PCA’s ability to detect underlying systematic change. RPCA is able to detect smaller systematic changes against the background of random fraction-to-fraction changes and is therefore more successful than SPCA at capturing systematic changes early in treatment. SPCA models were less successful at modeling systematic changes in clinical patient images, which contain a wider range of random motion than synthetic CBCTs, while the regularized approach was able to extract major modes of motion. Conclusions: Leading EDVFs from the both PCA approaches have the potential to capture systematic anatomical change during H&N radiotherapy when systematic changes are large enough with respect to random fraction-to-fraction changes. In all cases the RPCA approach appears to be more reliable at capturing systematic changes, enabling dosimetric consequences to be projected once trends are established early in a treatment course, or based on population models.« less

Phenotype analysis of early risk factors from electronic medical records improves image-derived diagnostic classifiers for optic nerve pathology

NASA Astrophysics Data System (ADS)

Chaganti, Shikha; Nabar, Kunal P.; Nelson, Katrina M.; Mawn, Louise A.; Landman, Bennett A.

2017-03-01

We examine imaging and electronic medical records (EMR) of 588 subjects over five major disease groups that affect optic nerve function. An objective evaluation of the role of imaging and EMR data in diagnosis of these conditions would improve understanding of these diseases and help in early intervention. We developed an automated image processing pipeline that identifies the orbital structures within the human eyes from computed tomography (CT) scans, calculates structural size, and performs volume measurements. We customized the EMR-based phenome-wide association study (PheWAS) to derive diagnostic EMR phenotypes that occur at least two years prior to the onset of the conditions of interest from a separate cohort of 28,411 ophthalmology patients. We used random forest classifiers to evaluate the predictive power of image-derived markers, EMR phenotypes, and clinical visual assessments in identifying disease cohorts from a control group of 763 patients without optic nerve disease. Image-derived markers showed more predictive power than clinical visual assessments or EMR phenotypes. However, the addition of EMR phenotypes to the imaging markers improves the classification accuracy against controls: the AUC improved from 0.67 to 0.88 for glaucoma, 0.73 to 0.78 for intrinsic optic nerve disease, 0.72 to 0.76 for optic nerve edema, 0.72 to 0.77 for orbital inflammation, and 0.81 to 0.85 for thyroid eye disease. This study illustrates the importance of diagnostic context for interpretation of image-derived markers and the proposed PheWAS technique provides a flexible approach for learning salient features of patient history and incorporating these data into traditional machine learning analyses.

Conservation and divergence of the cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) pathway in two plant-pathogenic fungi: Fusarium graminearum and F. verticillioides.

PubMed

Guo, Li; Breakspear, Andrew; Zhao, Guoyi; Gao, Lixin; Kistler, H Corby; Xu, Jin-Rong; Ma, Li-Jun

2016-02-01

The cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) pathway is a central signalling cascade that transmits extracellular stimuli and governs cell responses through the second messenger cAMP. The importance of cAMP signalling in fungal biology has been well documented and the key conserved components, adenylate cyclase (AC) and the catalytic subunit of PKA (CPKA), have been functionally characterized. However, other genes involved in this signalling pathway and their regulation are not well understood in filamentous fungi. Here, we performed a comparative transcriptomics analysis of AC and CPKA mutants in two closely related fungi: Fusarium graminearum (Fg) and F. verticillioides (Fv). Combining available Fg transcriptomics and phenomics data, we reconstructed the Fg cAMP signalling pathway. We developed a computational program that combines sequence conservation and patterns of orthologous gene expression to facilitate global transcriptomics comparisons between different organisms. We observed highly correlated expression patterns for most orthologues (80%) between Fg and Fv. We also identified a subset of 482 (6%) diverged orthologues, whose expression under all conditions was at least 50% higher in one genome than in the other. This enabled us to dissect the conserved and unique portions of the cAMP-PKA pathway. Although the conserved portions controlled essential functions, such as metabolism, the cell cycle, chromatin remodelling and the oxidative stress response, the diverged portions had species-specific roles, such as the production and detoxification of secondary metabolites unique to each species. The evolution of the cAMP-PKA signalling pathway seems to have contributed directly to fungal divergence and niche adaptation. © 2015 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.

Phenome-driven disease genetics prediction toward drug discovery.

PubMed

Chen, Yang; Li, Li; Zhang, Guo-Qiang; Xu, Rong

2015-06-15

Discerning genetic contributions to diseases not only enhances our understanding of disease mechanisms, but also leads to translational opportunities for drug discovery. Recent computational approaches incorporate disease phenotypic similarities to improve the prediction power of disease gene discovery. However, most current studies used only one data source of human disease phenotype. We present an innovative and generic strategy for combining multiple different data sources of human disease phenotype and predicting disease-associated genes from integrated phenotypic and genomic data. To demonstrate our approach, we explored a new phenotype database from biomedical ontologies and constructed Disease Manifestation Network (DMN). We combined DMN with mimMiner, which was a widely used phenotype database in disease gene prediction studies. Our approach achieved significantly improved performance over a baseline method, which used only one phenotype data source. In the leave-one-out cross-validation and de novo gene prediction analysis, our approach achieved the area under the curves of 90.7% and 90.3%, which are significantly higher than 84.2% (P < e(-4)) and 81.3% (P < e(-12)) for the baseline approach. We further demonstrated that our predicted genes have the translational potential in drug discovery. We used Crohn's disease as an example and ranked the candidate drugs based on the rank of drug targets. Our gene prediction approach prioritized druggable genes that are likely to be associated with Crohn's disease pathogenesis, and our rank of candidate drugs successfully prioritized the Food and Drug Administration-approved drugs for Crohn's disease. We also found literature evidence to support a number of drugs among the top 200 candidates. In summary, we demonstrated that a novel strategy combining unique disease phenotype data with system approaches can lead to rapid drug discovery. nlp. edu/public/data/DMN © The Author 2015. Published by Oxford University Press.

Comprehensive QTL mapping survey dissects the complex fruit texture physiology in apple (Malus x domestica Borkh.).

PubMed

Longhi, Sara; Moretto, Marco; Viola, Roberto; Velasco, Riccardo; Costa, Fabrizio

2012-02-01

Fruit ripening is a complex physiological process in plants whereby cell wall programmed changes occur mainly to promote seed dispersal. Cell wall modification also directly regulates the textural properties, a fundamental aspect of fruit quality. In this study, two full-sib populations of apple, with 'Fuji' as the common maternal parent, crossed with 'Delearly' and 'Pink Lady', were used to understand the control of fruit texture by QTL mapping and in silico gene mining. Texture was dissected with a novel high resolution phenomics strategy, simultaneously profiling both mechanical and acoustic fruit texture components. In 'Fuji × Delearly' nine linkage groups were associated with QTLs accounting from 15.6% to 49% of the total variance, and a highly significant QTL cluster for both textural components was mapped on chromosome 10 and co-located with Md-PG1, a polygalacturonase gene that, in apple, is known to be involved in cell wall metabolism processes. In addition, other candidate genes related to Md-NOR and Md-RIN transcription factors, Md-Pel (pectate lyase), and Md-ACS1 were mapped within statistical intervals. In 'Fuji × Pink Lady', a smaller set of linkage groups associated with the QTLs identified for fruit texture (15.9-34.6% variance) was observed. The analysis of the phenotypic variance over a two-dimensional PCA plot highlighted a transgressive segregation for this progeny, revealing two QTL sets distinctively related to both mechanical and acoustic texture components. The mining of the apple genome allowed the discovery of the gene inventory underlying each QTL, and functional profile assessment unravelled specific gene expression patterns of these candidate genes.

Phenotypic approaches to drought in cassava: review

PubMed Central

Okogbenin, Emmanuel; Setter, Tim L.; Ferguson, Morag; Mutegi, Rose; Ceballos, Hernan; Olasanmi, Bunmi; Fregene, Martin

2012-01-01

Cassava is an important crop in Africa, Asia, Latin America, and the Caribbean. Cassava can be produced adequately in drought conditions making it the ideal food security crop in marginal environments. Although cassava can tolerate drought stress, it can be genetically improved to enhance productivity in such environments. Drought adaptation studies in over three decades in cassava have identified relevant mechanisms which have been explored in conventional breeding. Drought is a quantitative trait and its multigenic nature makes it very challenging to effectively manipulate and combine genes in breeding for rapid genetic gain and selection process. Cassava has a long growth cycle of 12–18 months which invariably contributes to a long breeding scheme for the crop. Modern breeding using advances in genomics and improved genotyping, is facilitating the dissection and genetic analysis of complex traits including drought tolerance, thus helping to better elucidate and understand the genetic basis of such traits. A beneficial goal of new innovative breeding strategies is to shorten the breeding cycle using minimized, efficient or fast phenotyping protocols. While high throughput genotyping have been achieved, this is rarely the case for phenotyping for drought adaptation. Some of the storage root phenotyping in cassava are often done very late in the evaluation cycle making selection process very slow. This paper highlights some modified traits suitable for early-growth phase phenotyping that may be used to reduce drought phenotyping cycle in cassava. Such modified traits can significantly complement the high throughput genotyping procedures to fast track breeding of improved drought tolerant varieties. The need for metabolite profiling, improved phenomics to take advantage of next generation sequencing technologies and high throughput phenotyping are basic steps for future direction to improve genetic gain and maximize speed for drought tolerance breeding. PMID:23717282

Functionally Enigmatic Genes: A Case Study of the Brain Ignorome

PubMed Central

Pandey, Ashutosh K.; Lu, Lu; Wang, Xusheng; Homayouni, Ramin; Williams, Robert W.

2014-01-01

What proportion of genes with intense and selective expression in specific tissues, cells, or systems are still almost completely uncharacterized with respect to biological function? In what ways do these functionally enigmatic genes differ from well-studied genes? To address these two questions, we devised a computational approach that defines so-called ignoromes. As proof of principle, we extracted and analyzed a large subset of genes with intense and selective expression in brain. We find that publications associated with this set are highly skewed—the top 5% of genes absorb 70% of the relevant literature. In contrast, approximately 20% of genes have essentially no neuroscience literature. Analysis of the ignorome over the past decade demonstrates that it is stubbornly persistent, and the rapid expansion of the neuroscience literature has not had the expected effect on numbers of these genes. Surprisingly, ignorome genes do not differ from well-studied genes in terms of connectivity in coexpression networks. Nor do they differ with respect to numbers of orthologs, paralogs, or protein domains. The major distinguishing characteristic between these sets of genes is date of discovery, early discovery being associated with greater research momentum—a genomic bandwagon effect. Finally we ask to what extent massive genomic, imaging, and phenotype data sets can be used to provide high-throughput functional annotation for an entire ignorome. In a majority of cases we have been able to extract and add significant information for these neglected genes. In several cases—ELMOD1, TMEM88B, and DZANK1—we have exploited sequence polymorphisms, large phenome data sets, and reverse genetic methods to evaluate the function of ignorome genes. PMID:24523945

Functionally enigmatic genes: a case study of the brain ignorome.

PubMed

Pandey, Ashutosh K; Lu, Lu; Wang, Xusheng; Homayouni, Ramin; Williams, Robert W

2014-01-01

What proportion of genes with intense and selective expression in specific tissues, cells, or systems are still almost completely uncharacterized with respect to biological function? In what ways do these functionally enigmatic genes differ from well-studied genes? To address these two questions, we devised a computational approach that defines so-called ignoromes. As proof of principle, we extracted and analyzed a large subset of genes with intense and selective expression in brain. We find that publications associated with this set are highly skewed--the top 5% of genes absorb 70% of the relevant literature. In contrast, approximately 20% of genes have essentially no neuroscience literature. Analysis of the ignorome over the past decade demonstrates that it is stubbornly persistent, and the rapid expansion of the neuroscience literature has not had the expected effect on numbers of these genes. Surprisingly, ignorome genes do not differ from well-studied genes in terms of connectivity in coexpression networks. Nor do they differ with respect to numbers of orthologs, paralogs, or protein domains. The major distinguishing characteristic between these sets of genes is date of discovery, early discovery being associated with greater research momentum--a genomic bandwagon effect. Finally we ask to what extent massive genomic, imaging, and phenotype data sets can be used to provide high-throughput functional annotation for an entire ignorome. In a majority of cases we have been able to extract and add significant information for these neglected genes. In several cases--ELMOD1, TMEM88B, and DZANK1--we have exploited sequence polymorphisms, large phenome data sets, and reverse genetic methods to evaluate the function of ignorome genes.

Near-misses are an opportunity to improve patient safety: adapting strategies of high reliability organizations to healthcare.

PubMed

Van Spall, Harriette; Kassam, Alisha; Tollefson, Travis T

2015-08-01

Near-miss investigations in high reliability organizations (HROs) aim to mitigate risk and improve system safety. Healthcare settings have a higher rate of near-misses and subsequent adverse events than most high-risk industries, but near-misses are not systematically reported or analyzed. In this review, we will describe the strategies for near-miss analysis that have facilitated a culture of safety and continuous quality improvement in HROs. Near-miss analysis is routine and systematic in HROs such as aviation. Strategies implemented in aviation include the Commercial Aviation Safety Team, which undertakes systematic analyses of near-misses, so that findings can be incorporated into Standard Operating Procedures (SOPs). Other strategies resulting from incident analyses include Crew Resource Management (CRM) for enhanced communication, situational awareness training, adoption of checklists during operations, and built-in redundancy within systems. Health care organizations should consider near-misses as opportunities for quality improvement. The systematic reporting and analysis of near-misses, commonplace in HROs, can be adapted to health care settings to prevent adverse events and improve clinical outcomes.

Evaluating Web-Based Nursing Education's Effects: A Systematic Review and Meta-Analysis.

PubMed

Kang, Jiwon; Seomun, GyeongAe

2017-09-01

This systematic review and meta-analysis investigated whether using web-based nursing educational programs increases a participant's knowledge and clinical performance. We performed a meta-analysis of studies published between January 2000 and July 2016 and identified through RISS, CINAHL, ProQuest Central, Embase, the Cochrane Library, and PubMed. Eleven studies were eligible for inclusion in this analysis. The results of the meta-analysis demonstrated significant differences not only for the overall effect but also specifically for blended programs and short (2 weeks or 4 weeks) intervention periods. To present more evidence supporting the effectiveness of web-based nursing educational programs, further research is warranted.

Prevalence of Orofacial Clefts among Live Births in China: A Systematic Review and Meta-Analysis.

PubMed

Wang, Mengying; Yuan, Yuan; Wang, Zifan; Liu, Dongjing; Wang, Zhuqing; Sun, Feng; Wang, Ping; Zhu, Hongping; Li, Jing; Wu, Tao; Beaty, Terri H

2017-07-17

Orofacial clefts (OFCs) are common human birth defects in China. However, studies on the prevalence of OFCs present inconsistent results. The overall prevalence and geographic distribution of OFCs are poorly described in China. Thus, we conducted a systematic review and meta-analysis to estimate the prevalence of OFCs. The systematic review and meta-analysis were conducted on the basis of an established protocol (PROSPERO 2015: CRD42015030198). We systematically searched for articles in four electronic databases, including Embase, PubMed, Wanfang Database, and China National Knowledge Infrastructure (CNKI) to identify relevant studies about prevalence of OFCs in China. Meta-analysis, including subgroup analysis, was conducted to estimate the pooled prevalence. A total of 41 studies published between 1986 and 2015 were included in our analysis. The sample size ranged from 2,586 to 4,611,808 live births. The random-effects model of meta-analysis showed that the overall prevalence of OFCs in China was 1.4 per 1000 live births (95% confidence interval [CI], 1.1-1.7). In subgroup analysis based on geographic regions, we found that OFC prevalence in Southwest (2.3 per 1000 live births, 95% CI, 1.1-4.7) was higher than that in other regions of China. There were no significant time trends of OFCs during the study period (p-value = 0.47). The overall prevalence of OFCs in China was 1.4 per 1000 live births. No significant secular trend of prevalence has been found in this analysis. Further studies need to be conducted to explore the etiology of OFC to better control the risk of this common birth defect. Birth Defects Research 109:1011-1019, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Serum vitamin D levels in relation to schizophrenia: a systematic review and meta-analysis of observational studies.

PubMed

Valipour, Ghazaleh; Saneei, Parvane; Esmaillzadeh, Ahmad

2014-10-01

Although several observational studies have investigated the association between vitamin D status and schizophrenia, we are aware of no comprehensive meta-analysis in this regard. We aimed to conduct a systematic review and a meta-analysis of observational studies to summarize the available data on the association between serum vitamin D levels and schizophrenia. A systematic research on all published articles until October 2013 was conducted in PubMed, ISI (Web of science), SCOPUS, and Google Scholar. All observational studies that had measured serum vitamin D levels in schizophrenic patients were included in the systematic review. After considering exclusion criteria, we had 19 studies for the systematic review that were included in three separate meta-analyses: 1) a meta-analysis on mean levels of 25-hydroxyvitamin D [25(OH)D] (n = 13); 2) a meta-analysis on the prevalence of vitamin D deficiency (n = 8); 3) a meta-analysis on odds ratios (n = 8). Findings from a meta-analysis on means revealed that the overall mean difference in serum 25(OH)D levels between schizophrenic patients and control participants was -5.91 ng/mL [95% confidence interval (CI) -10.68, -1.14]. Subgroup analyses based on study design, the patient's hospitalization status, study quality, and study location did not explain between-study heterogeneity; however, type of biomarker assessed [25-hydroxyvitamin D3 vs 25-hydroxyvitamin D (D2 & D3)] could account for some degree of heterogeneity. RESULTS from the meta-analysis on the prevalence of vitamin D deficiency indicated that the overall prevalence of vitamin D deficiency in schizophrenic patients was 65.3% (95% CI 46.4%-84.2%). Findings from the meta-analysis on odds ratios indicated that vitamin D-deficient persons were 2.16 times (95% CI 1.32, 3.56) more likely to have schizophrenia than those with vitamin D sufficiency. No evidence of heterogeneity was detected. We found a strong association between vitamin D deficiency and schizophrenia. However, randomized clinical trials are required to confirm our findings.

Methodological quality evaluation of systematic reviews or meta-analyses on ERCC1 in non-small cell lung cancer: a systematic review.

PubMed

Tao, Huan; Zhang, Yueyuan; Li, Qian; Chen, Jin

2017-11-01

To assess the methodological quality of systematic reviews (SRs) or meta-analysis concerning the predictive value of ERCC1 in platinum chemotherapy of non-small cell lung cancer. We searched the PubMed, EMbase, Cochrane library, international prospective register of systematic reviews, Chinese BioMedical Literature Database, China National Knowledge Infrastructure, Wan Fang and VIP database for SRs or meta-analysis. The methodological quality of included literatures was evaluated by risk of bias in systematic review (ROBIS) scale. Nineteen eligible SRs/meta-analysis were included. The most frequently searched databases were EMbase (74%), PubMed, Medline and CNKI. Fifteen SRs did additional retrieval manually, but none of them retrieved the registration platform. 47% described the two-reviewers model in the screening for eligible original articles, and seven SRs described the two reviewers to extract data. In methodological quality assessment, inter-rater reliability Kappa was 0.87 between two reviewers. Research question were well related to all SRs in phase 1 and the eligibility criteria was suitable for each SR, and rated as 'low' risk bias. But the 'high' risk bias existed in all the SRs regarding methods used to identify and/or select studies, and data collection and study appraisal. More than two-third of SRs or meta-analysis were finished with high risk of bias in the synthesis, findings and the final phase. The study demonstrated poor methodological quality of SRs/meta-analysis assessing the predictive value of ERCC1 in chemotherapy among the NSCLC patients, especially the high performance bias. Registration or publishing the protocol is recommended in future research.

Capturing Public Opinion on Public Health Topics: A Comparison of Experiences from a Systematic Review, Focus Group Study, and Analysis of Online, User-Generated Content.

PubMed

Giles, Emma Louise; Adams, Jean M

2015-01-01

Capturing public opinion toward public health topics is important to ensure that services, policy, and research are aligned with the beliefs and priorities of the general public. A number of approaches can be used to capture public opinion. We are conducting a program of work on the effectiveness and acceptability of health promoting financial incentive interventions. We have captured public opinion on financial incentive interventions using three methods: a systematic review, focus group study, and analysis of online user-generated comments to news media reports. In this short editorial-style piece, we compare and contrast our experiences with these three methods. Each of these methods had their advantages and disadvantages. Advantages include tailoring of the research question for systematic reviews, probing of answers during focus groups, and the ability to aggregate a large data set using online user-generated content. However, disadvantages include needing to update systematic reviews, participants conforming to a dominant perspective in focus groups, and being unable to collect respondent characteristics during analysis of user-generated online content. That said, analysis of user-generated online content offers additional time and resource advantages, and we found it elicited similar findings to those obtained via more traditional methods, such as systematic reviews and focus groups. A number of methods for capturing public opinions on public health topics are available. Public health researchers, policy makers, and practitioners should choose methods appropriate to their aims. Analysis of user-generated online content, especially in the context of news media reports, may be a quicker and cheaper alternative to more traditional methods, without compromising on the breadth of opinions captured.

A Practical Guide to Conducting a Systematic Review and Meta-analysis of Health State Utility Values.

PubMed

Petrou, Stavros; Kwon, Joseph; Madan, Jason

2018-05-10

Economic analysts are increasingly likely to rely on systematic reviews and meta-analyses of health state utility values to inform the parameter inputs of decision-analytic modelling-based economic evaluations. Beyond the context of economic evaluation, evidence from systematic reviews and meta-analyses of health state utility values can be used to inform broader health policy decisions. This paper provides practical guidance on how to conduct a systematic review and meta-analysis of health state utility values. The paper outlines a number of stages in conducting a systematic review, including identifying the appropriate evidence, study selection, data extraction and presentation, and quality and relevance assessment. The paper outlines three broad approaches that can be used to synthesise multiple estimates of health utilities for a given health state or condition, namely fixed-effect meta-analysis, random-effects meta-analysis and mixed-effects meta-regression. Each approach is illustrated by a synthesis of utility values for a hypothetical decision problem, and software code is provided. The paper highlights a number of methodological issues pertinent to the conduct of meta-analysis or meta-regression. These include the importance of limiting synthesis to 'comparable' utility estimates, for example those derived using common utility measurement approaches and sources of valuation; the effects of reliance on limited or poorly reported published data from primary utility assessment studies; the use of aggregate outcomes within analyses; approaches to generating measures of uncertainty; handling of median utility values; challenges surrounding the disentanglement of utility estimates collected serially within the context of prospective observational studies or prospective randomised trials; challenges surrounding the disentanglement of intervention effects; and approaches to measuring model validity. Areas of methodological debate and avenues for future research are highlighted.

The effectiveness of concept mapping on development of critical thinking in nursing education: A systematic review and meta-analysis.

PubMed

Yue, Meng; Zhang, Meng; Zhang, Chunmei; Jin, Changde

2017-05-01

As an essential skill in daily clinical nursing practice, critical thinking ability has been an important objective in nursing education. Concept mapping enables nursing students connect new information to existing knowledge and integrates interdisciplinary knowledge. However, there is a lack of evidence related to critical thinking ability and concept mapping in nursing education. The purpose of this systematic review and meta-analysis was to assess the effect of concept mapping in developing critical thinking in nursing education. This systematic review was reported in line with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). A search was conducted in PubMed, Web of science, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health (CINAHL) and China National Knowledge Infrastructure (CNKI). Randomized controlled trials (RCT) comparing concept mapping and traditional teaching method were retrieved. Data were collected by two reviewers according to the data extraction tables. The methodological quality of included studies was assessed by other two reviewers. The results of meta-analysis were presented using mean difference (MD). Thirteen trials were summarized in the systematic review and eleven trials were included in the meta-analysis. The pooled effect size showed that, comparing with traditional methods, concept mapping could improve subjects' critical thinking ability measured by California Critical Thinking Disposition Inventory (CCTDI), California Critical Thinking Skill Test (CCTST) and Critical Thinking Scale (CTS). The subgroup analyses showed that concept mapping improved the score of all subscales. The result of this review indicated that concept mapping could affect the critical thinking affective dispositions and critical thinking cognitive skills. Further high quality research using uniform evaluation is required. Copyright © 2017 Elsevier Ltd. All rights reserved.

Association between long travel and venous thromboembolic disease: a systematic review and meta-analysis of case-control studies

PubMed Central

Jiménez-Puente, Alberto; Perea-Milla, Emilio

2007-01-01

The term “economy-class syndrome” defines an infrequent episode of venous thromboembolism (VTED) related to a long travel, namely by plane. However, this relation has not clearly been demonstrated by investigators. We carried out a systematic review and a meta-analysis of cases-control studies that had studied this topic. We realised a systematic review of the literature and selected all the case-control studies published. Two authors carried out a methodological evaluation according to the Scottish Intercollegiate Guidelines Network items (concordance was analysed by weighted kappa index), and a systematic analysis of the potential biases of each study was assessed. We carried out the meta-analysis with the data extracted from the studies. We recovered eight cases-control studies. The relation between the antecedent of a long travel and subsequent VTED varied from OR = 1.1 to OR = 4.0 and was found to be significant in four studies. The studies were highly heterogeneous in methodology and so the results obtained about the relation between the long travel and the VTED and the score at SIGN50. Two meta-analysis were carried out: only with travels by plane in which the relation was not significant (OR = 1.21; CI 95%, 0.95–1.55) and with all types of transport, with a slightly significant relation (OR = 1.46; CI95%, 1.24–1.72). We may deduce from this systematic review that there does exist a weak association between episodes of VTED and a long travel, but not by plane specifically. The heterogeneity and the methodological quality of the studies published preclude of more robust conclusions. PMID:17899081

Increased prevalence of anxiety symptoms in women with polycystic ovary syndrome: systematic review and meta-analysis.

PubMed

Dokras, Anuja; Clifton, Shari; Futterweit, Walter; Wild, Robert

2012-01-01

To perform a systematic review and meta-analysis of studies that compared the prevalence of anxiety symptoms in women with polycystic ovary syndrome (PCOS) and control women. Meta-analysis and systematic review. University practice. Cross-sectional studies comparing PCOS subjects and geographically matched clearly defined non-PCOS control subjects with data on age and body mass index (BMI). Anxiety screening tool. The primary analysis contrasted prevalence of anxiety. Cochrane Review Manager 5.0.24 software was used to construct forest plots comparing frequency of anxiety symptoms in case and control subjects. Of 613 screened articles, nine met our selection criteria for a systematic review and four were included in the meta-analysis. The prevalence of generalized anxiety symptoms was available in four studies and was significantly greater in PCOS subjects (42/206, 20.4%) compared to controls (8/204, 3.9%). The odds for anxiety symptoms were significantly greater in women with PCOS compared with control subjects (odds ratio 6.88, 95% confidence interval 2.5-18.9). The mean anxiety score was significantly increased in three of the remaining five studies. Other anxiety disorders, such as social phobia, panic attacks, and obsessive compulsive disorders, were assessed infrequently. Our systematic review suggests an increased odds of anxiety symptoms in women with PCOS, underscoring the importance of screening all women with PCOS for anxiety symptoms. Follow-up evaluation and treatment are essential, because generalized anxiety disorder is a chronic condition. Potential contributors for anxiety symptoms, such as hirsutism, obesity, and/or infertility may be specific to women with PCOS but need further investigation. Copyright © 2012. Published by Elsevier Inc.

Prevalence of nephropathy in type 1 diabetes in the Arab world: A systematic review and meta-analysis.

PubMed

Abdel-Motal, Ussama M; G, Akila; Abdelalim, Essam M; Ponnuraja, Chinnaiyan; Iken, Khadija; Jahromi, Mohamed; Doss, George Priya; El Bekay, Rajaa; Zayed, Hatem

2018-05-17

The aim of this study was to conduct a systematic review and meta-analysis and determine the prevalence of diabetic nephropathy (DN) among Arab patients with T1D. A systematic literature search was conducted using 4 different literature databases (PubMed, ScienceDirect, Web of Science, and Embase) to capture all relevant data about Arab patients with T1D that had DN. Meta-analysis and systematic review were performed using the random effect model, and the heterogeneity of the studies was assessed using the Q-test, I2, and Tau-squared statistics. Publication bias was assessed using the funnel-plot test. Our search strategy captured 372 studies in only 10 out of the 22 Arab countries in a period of 48 years (1969-2017); of which, 41 met our inclusion criteria for full article analysis, of those, 15 were eligible for meta-analysis. We estimated the prevalence of DN among Arab people with T1D to be 18.2% (95% confidence interval 13.1%-24.8%). In conclusion, DN prevalence is underexplored among Arab patients with T1D and represents a significant risk for the well-being of Arab patients with T1D. Therefore, there is an urgent need for comprehensive epidemiological studies for DN among Arab patients with T1D. Copyright © 2018 John Wiley & Sons, Ltd.

Association between depression and periodontitis: a systematic review and meta-analysis.

PubMed

Araújo, Milena Moreira; Martins, Carolina Castro; Costa, Lidiane Cristina Machado; Cota, Luís Otávio Miranda; Faria, Rodrigo Lamounier Araújo Melo; Cunha, Fabiano Araújo; Costa, Fernando Oliveira

2016-03-01

The aim of this systematic review and meta-analysis was to assess the scientific evidence on the association between depression and periodontitis. An electronic search was conducted in three databases until October 2015 (PROSPERO-CRD42014006451). Hand searches and grey literature were also included. Search retrieved 423 potentially studies. Two independent reviewers selected the studies, extracted data and assessed risk bias through a modified version of Newcastle-Ottawa scale. Meta-analysis was performed for the presence/absence of periodontitis (dichotomic). Summary effect measures and odds ratio (OR) 95% CI were calculated. After selecting the studies, 15 were included in the systematic review (eight cross-sectional, six case-control and one cohort study). Six studies reported that depression was associated with periodontitis, whereas nine studies did not. The majority of studies had low risk of bias by methodological quality assessment. Meta-analysis of seven cross-sectional studies showed no significant association between depression and periodontitis (OR = 1.03, 95% CI = 0.75-1.41). Findings from the present systematic review showed a great heterogeneity among the studies and the summary effect measure of the meta-analysis cannot affirm an association between depression and periodontitis. Future studies with different designs in distinct populations should be conducted to investigate this association. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Can we discover double Higgs production at the LHC?

NASA Astrophysics Data System (ADS)

Alves, Alexandre; Ghosh, Tathagata; Sinha, Kuver

2017-08-01

We explore double Higgs production via gluon fusion in the b b ¯γ γ channel at the high-luminosity LHC using machine learning tools. We first propose a Bayesian optimization approach to select cuts on kinematic variables, obtaining a 30%-50% increase in the significance compared to current results in the literature. We show that this improvement persists once systematic uncertainties are taken into account. We next use boosted decision trees (BDT) to further discriminate signal and background events. Our analysis shows that a joint optimization of kinematic cuts and BDT hyperparameters results in an appreciable improvement in the significance. Finally, we perform a multivariate analysis of the output scores of the BDT. We find that assuming a very low level of systematics, the techniques proposed here will be able to confirm the production of a pair of standard model Higgs bosons at 5 σ level with 3 ab-1 of data. Assuming a more realistic projection of the level of systematics, around 10%, the optimization of cuts to train BDTs combined with a multivariate analysis delivers a respectable significance of 4.6 σ . Even assuming large systematics of 20%, our analysis predicts a 3.6 σ significance, which represents at least strong evidence in favor of double Higgs production. We carefully incorporate background contributions coming from light flavor jets or c jets being misidentified as b jets and jets being misidentified as photons in our analysis.

Interpretive analysis of 85 systematic reviews suggests that narrative syntheses and meta-analyses are incommensurate in argumentation.

PubMed

Melendez-Torres, G J; O'Mara-Eves, A; Thomas, J; Brunton, G; Caird, J; Petticrew, M

2017-03-01

Using Toulmin's argumentation theory, we analysed the texts of systematic reviews in the area of workplace health promotion to explore differences in the modes of reasoning embedded in reports of narrative synthesis as compared with reports of meta-analysis. We used framework synthesis, grounded theory and cross-case analysis methods to analyse 85 systematic reviews addressing intervention effectiveness in workplace health promotion. Two core categories, or 'modes of reasoning', emerged to frame the contrast between narrative synthesis and meta-analysis: practical-configurational reasoning in narrative synthesis ('what is going on here? What picture emerges?') and inferential-predictive reasoning in meta-analysis ('does it work, and how well? Will it work again?'). Modes of reasoning examined quality and consistency of the included evidence differently. Meta-analyses clearly distinguished between warrant and claim, whereas narrative syntheses often presented joint warrant-claims. Narrative syntheses and meta-analyses represent different modes of reasoning. Systematic reviewers are likely to be addressing research questions in different ways with each method. It is important to consider narrative synthesis in its own right as a method and to develop specific quality criteria and understandings of how it is carried out, not merely as a complement to, or second-best option for, meta-analysis. © 2016 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd. © 2016 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd.

The full spectrum of ethical issues in the care of patients with ALS: a systematic qualitative review.

PubMed

Seitzer, F; Kahrass, H; Neitzke, G; Strech, D

2016-02-01

Dealing systematically with ethical issues in amyotrophic lateral sclerosis (ALS) care requires an unbiased awareness of all the relevant ethical issues. The aim of the study was to determine systematically and transparently the full spectrum of ethical issues in ALS care. We conducted a systematic review in Medline and Google Books (restricted to English and German literature published between 1993 and 2014). We applied qualitative text analysis and normative analysis to categorise the spectrum of ethical issues in ALS care. The literature review retrieved 56 references that together mentioned a spectrum of 103 ethical issues in ALS care. The spectrum was structured into six major categories that consist of first and second-order categories of ethical issues. The systematically derived spectrum of ethical issues in ALS care presented in this paper raises awareness and understanding of the complexity of ethical issues in ALS care. It also offers a basis for the systematic development of informational and training materials for health professionals, patients and their relatives, and society as a whole. Finally, it supports a rational and fair selection of all those ethical issues that should be addressed in health policies, position papers and clinical practice guidelines. Further research is needed to identify ways to systematically select the most relevant ethical issues not only in the clinical environment, but also for the development of clinical practice guidelines.

A systematic review of training programs for parents of children with autism spectrum disorders: single subject contributions.

PubMed

Patterson, Stephanie Y; Smith, Veronica; Mirenda, Pat

2012-09-01

The purpose of this systematic review was to examine research utilizing single subject research designs (SSRD) to explore the effectiveness of interventions designed to increase parents' ability to support communication and social development in children with autism spectrum disorders (ASDs). Included studies were systematically assessed for methodological quality (Logan et al., 2008; Smith et al., 2007) and intervention effects. Data examining participant characteristics, study methodology, outcomes, and analysis were systematically extracted. Eleven SSRD parent-training intervention studies examining 44 participants with ASD were included. Overall, the studies were of moderate quality and reported increases in parent skills and child language and communication outcomes. The results supported by improvement rate difference (IRD) analysis indicated several interventions demonstrated positive effects for both parent and child outcomes. However, limited generalization and follow-up data suggested only one intervention demonstrated parents' accurate and ongoing intervention implementation beyond training.

Effect of exercise on cognitive function in chronic disease patients: a meta-analysis and systematic review of randomized controlled trials

PubMed Central

Cai, Hong; Li, Guichen; Hua, Shanshan; Liu, Yufei; Chen, Li

2017-01-01

Background The purpose of this study was to conduct a meta-analysis and systematic review to assess the effect of exercise on cognitive function in people with chronic diseases. Methods PubMed, Web of Science, Embase, the Cochrane Library, CINAHL, PsycINFO, and three Chinese databases were electronically searched for papers that were published until September 2016. This meta-analysis and systematic review included randomized controlled trials that evaluated the effect of exercise on cognitive function compared with control group for people with chronic diseases. Results Totally, 35 studies met the inclusion criteria, with 3,113 participants. The main analysis revealed a positive overall random effect of exercise intervention on cognitive function in patients with chronic diseases. The secondary analysis revealed that aerobic exercise interventions and aerobic included exercise interventions had a positive effect on cognition in patients with chronic diseases. The intervention offering low frequency had a positive effect on cognitive function in patients with chronic diseases. Finally, we found that interventions offered at both low exercise intensity and moderate exercise intensity had a positive effect on cognitive function in patients with chronic diseases. The secondary analysis also revealed that exercise interventions were beneficial in Alzheimer’s disease patients when grouped by disease type. Conclusion This meta-analysis and systematic review suggests that exercise interventions positively influence cognitive function in patients with chronic diseases. Beneficial effect was independent of the type of disease, type of exercise, frequency, and the intensity of the exercise intervention. PMID:28546744

Effects of After-School Programs on Attendance and Externalizing Behaviors with Primary and Secondary School Students: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Maynard, Brandy R.; Kremer, Kristen P.; Polanin, Joshua R.; Vaughn, Michael G.; Sarteschi, Christine M.

2015-01-01

Over the past two decades, the number and types of after-school programs (ASPs) have increased substantially as a result of increased federal and private spending and because ASPs are perceived to provide wide-ranging and far-reaching benefits to students, families, schools and the public. The purpose of this systematic review and meta-analysis is…

To the systematization of failure analysis for perturbed systems (in German)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haller, U.

1974-01-01

The paper investigates the reliable functioning of complex technical systems. Of main importance is the question of how the functioning of technical systems which may fail or whose design still has some faults can be determined in the very earliest planning stages. The present paper is to develop a functioning schedule and to look for possible methods of systematic failure analysis of systems with stochastic failures. (RW/AK)

[Long-term use of mobile phone and its association with glioma: a systematic review and meta-analysis].

PubMed

Gong, Xiu; Wu, Jinsong; Mao, Ying; Zhou, Liangfu

2014-10-28

The hypothesis that "cell phone induces brain tumor" has become a target of much controversy for several decades and is still a matter of debate even now. We aim to make a systematic review and meta-analysis based on published studies on glioma to identify current evidences for evaluating mobile phones and glioma risk, especially on long-term use of mobile phones. The study was conducted according to the Cochrane systematic review methods and reported according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) statement according to a prospective research protocol accessed via http://www.crd.york.ac.uk/prospero. The software RevMan 5 was used for statistic analysis. Latency and lateralization were used for the examining the dose-response relationship. Overall evidence suggested the increased risk of glioma among long-term ipsilateral users of mobile phone with an odds ratio (OR) of 1.46[1.12, 1.92] based on meta-analysis. Especially, for low-grade glioma, long-term use yielded an OR value of 2.27 [1.81, 2.85]. The evidence is currently insufficient on this issue, especially on long-term use of mobile phone. Neither a definite answer nor a clear explanation may be offered for the relationship. And larger prospective trials are warranted.

Methodological issues and recommendations for systematic reviews of prognostic studies: an example from cardiovascular disease.

PubMed

Dretzke, Janine; Ensor, Joie; Bayliss, Sue; Hodgkinson, James; Lordkipanidzé, Marie; Riley, Richard D; Fitzmaurice, David; Moore, David

2014-12-03

Prognostic factors are associated with the risk of future health outcomes in individuals with a particular health condition. The prognostic ability of such factors is increasingly being assessed in both primary research and systematic reviews. Systematic review methodology in this area is continuing to evolve, reflected in variable approaches to key methodological aspects. The aim of this article was to (i) explore and compare the methodology of systematic reviews of prognostic factors undertaken for the same clinical question, (ii) to discuss implications for review findings, and (iii) to present recommendations on what might be considered to be 'good practice' approaches. The sample was comprised of eight systematic reviews addressing the same clinical question, namely whether 'aspirin resistance' (a potential prognostic factor) has prognostic utility relative to future vascular events in patients on aspirin therapy for secondary prevention. A detailed comparison of methods around study identification, study selection, quality assessment, approaches to analysis, and reporting of findings was undertaken and the implications discussed. These were summarised into key considerations that may be transferable to future systematic reviews of prognostic factors. Across systematic reviews addressing the same clinical question, there were considerable differences in the numbers of studies identified and overlap between included studies, which could only partially be explained by different study eligibility criteria. Incomplete reporting and differences in terminology within primary studies hampered study identification and selection process across reviews. Quality assessment was highly variable and only one systematic review considered a checklist for studies of prognostic questions. There was inconsistency between reviews in approaches towards analysis, synthesis, addressing heterogeneity and reporting of results. Different methodological approaches may ultimately affect the findings and interpretation of systematic reviews of prognostic research, with implications for clinical decision-making.

Analysis of Existing Guidelines for the Systematic Planning Process of Clinical Registries.

PubMed

Löpprich, Martin; Knaup, Petra

2016-01-01

Clinical registries are a powerful method to observe the clinical practice and natural disease history. In contrast to clinical trials, where guidelines and standardized methods exist and are mandatory, only a few initiatives have published methodological guidelines for clinical registries. The objective of this paper was to review these guidelines and systematically assess their completeness, usability and feasibility according to a SWOT analysis. The results show that each guideline has its own strengths and weaknesses. While one supports the systematic planning process, the other discusses clinical registries in great detail. However, the feasibility was mostly limited and the special requirements of clinical registries, their flexible, expandable and adaptable technological structure was not addressed consistently.

Directional variance adjustment: bias reduction in covariance matrices based on factor analysis with an application to portfolio optimization.

PubMed

Bartz, Daniel; Hatrick, Kerr; Hesse, Christian W; Müller, Klaus-Robert; Lemm, Steven

2013-01-01

Robust and reliable covariance estimates play a decisive role in financial and many other applications. An important class of estimators is based on factor models. Here, we show by extensive Monte Carlo simulations that covariance matrices derived from the statistical Factor Analysis model exhibit a systematic error, which is similar to the well-known systematic error of the spectrum of the sample covariance matrix. Moreover, we introduce the Directional Variance Adjustment (DVA) algorithm, which diminishes the systematic error. In a thorough empirical study for the US, European, and Hong Kong stock market we show that our proposed method leads to improved portfolio allocation.

Directional Variance Adjustment: Bias Reduction in Covariance Matrices Based on Factor Analysis with an Application to Portfolio Optimization

PubMed Central

Bartz, Daniel; Hatrick, Kerr; Hesse, Christian W.; Müller, Klaus-Robert; Lemm, Steven

2013-01-01

Robust and reliable covariance estimates play a decisive role in financial and many other applications. An important class of estimators is based on factor models. Here, we show by extensive Monte Carlo simulations that covariance matrices derived from the statistical Factor Analysis model exhibit a systematic error, which is similar to the well-known systematic error of the spectrum of the sample covariance matrix. Moreover, we introduce the Directional Variance Adjustment (DVA) algorithm, which diminishes the systematic error. In a thorough empirical study for the US, European, and Hong Kong stock market we show that our proposed method leads to improved portfolio allocation. PMID:23844016

Note of the methodological flaws in the paper entitled "GSTT1 and GSTM1 polymorphisms predict treatment outcome for breast cancer: a systematic review and meta-analysis".

PubMed

Qiu, Mali; Wu, Xu; Qu, Xiaobing

2016-09-01

With great interest, we read the paper "GSTT1 and GSTM1 polymorphisms predict treatment outcome for breast cancer: a systematic review and meta-analysis" (by Hu XY et al.), which has reached important conclusions that GSTM1 null and GSTT1/GSTM1 double null polymorphisms might be significantly associated with an increased tumor response in breast cancer. The result is encouraging. Nevertheless, several methodological flaws in this meta-analysis are worth noticing.

Exploring cosmic origins with CORE: Mitigation of systematic effects

NASA Astrophysics Data System (ADS)

Natoli, P.; Ashdown, M.; Banerji, R.; Borrill, J.; Buzzelli, A.; de Gasperis, G.; Delabrouille, J.; Hivon, E.; Molinari, D.; Patanchon, G.; Polastri, L.; Tomasi, M.; Bouchet, F. R.; Henrot-Versillé, S.; Hoang, D. T.; Keskitalo, R.; Kiiveri, K.; Kisner, T.; Lindholm, V.; McCarthy, D.; Piacentini, F.; Perdereau, O.; Polenta, G.; Tristram, M.; Achucarro, A.; Ade, P.; Allison, R.; Baccigalupi, C.; Ballardini, M.; Banday, A. J.; Bartlett, J.; Bartolo, N.; Basak, S.; Baumann, D.; Bersanelli, M.; Bonaldi, A.; Bonato, M.; Boulanger, F.; Brinckmann, T.; Bucher, M.; Burigana, C.; Cai, Z.-Y.; Calvo, M.; Carvalho, C.-S.; Castellano, M. G.; Challinor, A.; Chluba, J.; Clesse, S.; Colantoni, I.; Coppolecchia, A.; Crook, M.; D'Alessandro, G.; de Bernardis, P.; De Zotti, G.; Di Valentino, E.; Diego, J.-M.; Errard, J.; Feeney, S.; Fernandez-Cobos, R.; Finelli, F.; Forastieri, F.; Galli, S.; Genova-Santos, R.; Gerbino, M.; González-Nuevo, J.; Grandis, S.; Greenslade, J.; Gruppuso, A.; Hagstotz, S.; Hanany, S.; Handley, W.; Hernandez-Monteagudo, C.; Hervías-Caimapo, C.; Hills, M.; Keihänen, E.; Kitching, T.; Kunz, M.; Kurki-Suonio, H.; Lamagna, L.; Lasenby, A.; Lattanzi, M.; Lesgourgues, J.; Lewis, A.; Liguori, M.; López-Caniego, M.; Luzzi, G.; Maffei, B.; Mandolesi, N.; Martinez-González, E.; Martins, C. J. A. P.; Masi, S.; Matarrese, S.; Melchiorri, A.; Melin, J.-B.; Migliaccio, M.; Monfardini, A.; Negrello, M.; Notari, A.; Pagano, L.; Paiella, A.; Paoletti, D.; Piat, M.; Pisano, G.; Pollo, A.; Poulin, V.; Quartin, M.; Remazeilles, M.; Roman, M.; Rossi, G.; Rubino-Martin, J.-A.; Salvati, L.; Signorelli, G.; Tartari, A.; Tramonte, D.; Trappe, N.; Trombetti, T.; Tucker, C.; Valiviita, J.; Van de Weijgaert, R.; van Tent, B.; Vennin, V.; Vielva, P.; Vittorio, N.; Wallis, C.; Young, K.; Zannoni, M.

2018-04-01

We present an analysis of the main systematic effects that could impact the measurement of CMB polarization with the proposed CORE space mission. We employ timeline-to-map simulations to verify that the CORE instrumental set-up and scanning strategy allow us to measure sky polarization to a level of accuracy adequate to the mission science goals. We also show how the CORE observations can be processed to mitigate the level of contamination by potentially worrying systematics, including intensity-to-polarization leakage due to bandpass mismatch, asymmetric main beams, pointing errors and correlated noise. We use analysis techniques that are well validated on data from current missions such as Planck to demonstrate how the residual contamination of the measurements by these effects can be brought to a level low enough not to hamper the scientific capability of the mission, nor significantly increase the overall error budget. We also present a prototype of the CORE photometric calibration pipeline, based on that used for Planck, and discuss its robustness to systematics, showing how CORE can achieve its calibration requirements. While a fine-grained assessment of the impact of systematics requires a level of knowledge of the system that can only be achieved in a future study phase, the analysis presented here strongly suggests that the main areas of concern for the CORE mission can be addressed using existing knowledge, techniques and algorithms.

Prevalence of Celiac Disease in Latin America: A Systematic Review and Meta-Regression

PubMed Central

Parra-Medina, Rafael; Molano-Gonzalez, Nicolás; Rojas-Villarraga, Adriana; Agmon-Levin, Nancy; Arango, Maria-Teresa; Shoenfeld, Yehuda; Anaya, Juan-Manuel

2015-01-01

Background Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten in susceptible individuals, and its prevalence varies depending on the studied population. Given that information on CD in Latin America is scarce, we aimed to investigate the prevalence of CD in this region of the world through a systematic review and meta-analysis. Methods and Findings This was a two-phase study. First, a cross-sectional analysis from 981 individuals of the Colombian population was made. Second, a systematic review and meta-regression analysis were performed following the Preferred Reporting Items for Systematic Meta- Analyses (PRISMA) guidelines. Our results disclosed a lack of celiac autoimmunity in the studied Colombian population (i.e., anti-tissue transglutaminase (tTG) and IgA anti-endomysium (EMA)). In the systematic review, 72 studies were considered. The estimated prevalence of CD in Latin Americans ranged between 0.46% and 0.64%. The prevalence of CD in first-degree relatives of CD probands was 5.5%. The coexistence of CD and type 1 diabetes mellitus varied from 4.6% to 8.7%, depending on the diagnosis methods (i.e., autoantibodies and/or biopsies). Conclusions Although CD seems to be a rare condition in Colombians; the general prevalence of the disease in Latin Americans seemingly corresponds to a similar scenario observed in Europeans. PMID:25942408

Frailty as a Predictor of Alzheimer Disease, Vascular Dementia, and All Dementia Among Community-Dwelling Older People: A Systematic Review and Meta-Analysis.

PubMed

Kojima, Gotaro; Taniguchi, Yu; Iliffe, Steve; Walters, Kate

2016-10-01

To perform a systematic search of the literature for currently available evidence on frailty as a predictor of dementia and to conduct a meta-analysis to synthesize the pooled risk estimates among community-dwelling older people. A systematic review and meta-analysis. Embase, MEDLINE, CINAHL Plus, PsycINFO, and the Cochrane Library from 2000 to January 2016, and reference lists of relevant articles. Any studies that prospectively examined the incident risks of dementia with frailty among community-dwelling older people without language restriction. Of 2565 studies identified through the systematic review, 7 studies were included in this review. Of these, 4 studies reported hazard ratios (HR) of incident dementia for physical frailty defined by Cardiovascular Health Study criteria and were included in a meta-analysis. Frailty was a significant predictor of incident Alzheimer disease (4 studies: pooled HR = 1.28, 95% confidence interval (95% CI) = 1.00-1.63, P = .05), vascular dementia (2 studies: pooled HR 2.70, 95% CI 1.40-5.23, P = .003), and all dementia (3 studies: pooled HR 1.33, 95% CI 1.07-1.67, P = .01). Heterogeneity across the studies was low to modest (I(2) = 0%-51%). A random-effects meta-regression analysis showed that the female proportion of the cohort primarily mediated the association of frailty with Alzheimer disease (female proportion coefficient = 0.04, 95%CI = 0.01-0.08, P = .01). This systematic review and meta-analysis suggests that frailty was a significant predictor of Alzheimer disease, vascular dementia, and all dementia among community-dwelling older people. Frail women may have a higher risk of incident Alzheimer disease than frail men. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Citation of previous meta-analyses on the same topic: a clue to perpetuation of incorrect methods?

PubMed

Li, Tianjing; Dickersin, Kay

2013-06-01

Systematic reviews and meta-analyses serve as a basis for decision-making and clinical practice guidelines and should be carried out using appropriate methodology to avoid incorrect inferences. We describe the characteristics, statistical methods used for meta-analyses, and citation patterns of all 21 glaucoma systematic reviews we identified pertaining to the effectiveness of prostaglandin analog eye drops in treating primary open-angle glaucoma, published between December 2000 and February 2012. We abstracted data, assessed whether appropriate statistical methods were applied in meta-analyses, and examined citation patterns of included reviews. We identified two forms of problematic statistical analyses in 9 of the 21 systematic reviews examined. Except in 1 case, none of the 9 reviews that used incorrect statistical methods cited a previously published review that used appropriate methods. Reviews that used incorrect methods were cited 2.6 times more often than reviews that used appropriate statistical methods. We speculate that by emulating the statistical methodology of previous systematic reviews, systematic review authors may have perpetuated incorrect approaches to meta-analysis. The use of incorrect statistical methods, perhaps through emulating methods described in previous research, calls conclusions of systematic reviews into question and may lead to inappropriate patient care. We urge systematic review authors and journal editors to seek the advice of experienced statisticians before undertaking or accepting for publication a systematic review and meta-analysis. The author(s) have no proprietary or commercial interest in any materials discussed in this article. Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Is computer-assisted instruction more effective than other educational methods in achieving ECG competence among medical students and residents? Protocol for a systematic review and meta-analysis.

PubMed

Viljoen, Charle André; Scott Millar, Rob; Engel, Mark E; Shelton, Mary; Burch, Vanessa

2017-12-26

Although ECG interpretation is an essential skill in clinical medicine, medical students and residents often lack ECG competence. Novel teaching methods are increasingly being implemented and investigated to improve ECG training. Computer-assisted instruction is one such method under investigation; however, its efficacy in achieving better ECG competence among medical students and residents remains uncertain. This article describes the protocol for a systematic review and meta-analysis that will compare the effectiveness of computer-assisted instruction with other teaching methods used for the ECG training of medical students and residents. Only studies with a comparative research design will be considered. Articles will be searched for in electronic databases (PubMed, Scopus, Web of Science, Academic Search Premier, CINAHL, PsycINFO, Education Resources Information Center, Africa-Wide Information and Teacher Reference Center). In addition, we will review citation indexes and conduct a grey literature search. Data extraction will be done on articles that met the predefined eligibility criteria. A descriptive analysis of the different teaching modalities will be provided and their educational impact will be assessed in terms of effect size and the modified version of Kirkpatrick framework for the evaluation of educational interventions. This systematic review aims to provide evidence as to whether computer-assisted instruction is an effective teaching modality for ECG training. It is hoped that the information garnered from this systematic review will assist in future curricular development and improve ECG training. As this research is a systematic review of published literature, ethical approval is not required. The results will be reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement and will be submitted to a peer-reviewed journal. The protocol and systematic review will be included in a PhD dissertation. CRD42017067054; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The Quality of Systematic Reviews in Head and Neck Microsurgery: A Perspective from Plastic Surgery and Otolaryngology.

PubMed

Sun, Beatrice J; Tijerina, Jonathan; Nazerali, Rahim S; Lee, Gordon K

2018-05-01

In recent years, there has been a push to publish higher level of evidence studies in medicine, particularly in plastic surgery. Well-conducted systematic reviews are considered the strongest level of evidence in medicine, recently becoming the key process indicators for quality delivery. A varying quality of systematic reviews, however, has led to concerns of their validity in clinical decision-making. We perform a quality analysis of systematic reviews published in head and neck microsurgery by the surgical specialties of plastic surgery and otolaryngology. An evaluation of systematic reviews published on microsurgery in 13 high-impact surgical journals was conducted by searching PubMed and Scopus. Two authors independently performed searches, screened for eligibility, and extracted data from included articles. Discrepancies were resolved by discussion and consensus. Assessment of Multiple Systematic Reviews (AMSTAR) criteria were used to assess methodological quality. The initial database search retrieved 166 articles. After removing duplicates, screening titles and abstracts, 26 articles remained for full text review. Seven did not focus on head and neck microsurgery and were further excluded, leaving 19 systematic reviews for final analysis. Of those, 10 systematic reviews were published by otolaryngology, and 9 were published by plastic surgery. Median AMSTAR score was 8 for otolaryngology, 7 for plastic surgery, and 8 overall, reflecting "fair to good" quality. The number of systematic reviews on head and neck microsurgery markedly increased over time. Of note, both the AMSTAR score and the number of systematic reviews published by plastic surgery have steadily increased from 2014 to 2016, whereas those published by otolaryngology have remained relatively stable since 2010. Our review shows a trend toward publishing more systematic reviews. The increasing quantity and quality of systematic reviews published by plastic surgeons indicates recognition in the need for higher levels of evidence in plastic surgery, as well as growing interest and advances in microsurgery. Given these trends, familiarity with quality assessment guidelines, such as AMSTAR, will remain important in providing a basis for building relevant value-based quality measures.

Requirements analysis, domain knowledge, and design

NASA Technical Reports Server (NTRS)

Potts, Colin

1988-01-01

Two improvements to current requirements analysis practices are suggested: domain modeling, and the systematic application of analysis heuristics. Domain modeling is the representation of relevant application knowledge prior to requirements specification. Artificial intelligence techniques may eventually be applicable for domain modeling. In the short term, however, restricted domain modeling techniques, such as that in JSD, will still be of practical benefit. Analysis heuristics are standard patterns of reasoning about the requirements. They usually generate questions of clarification or issues relating to completeness. Analysis heuristics can be represented and therefore systematically applied in an issue-based framework. This is illustrated by an issue-based analysis of JSD's domain modeling and functional specification heuristics. They are discussed in the context of the preliminary design of simple embedded systems.

Data extraction for complex meta-analysis (DECiMAL) guide.

PubMed

Pedder, Hugo; Sarri, Grammati; Keeney, Edna; Nunes, Vanessa; Dias, Sofia

2016-12-13

As more complex meta-analytical techniques such as network and multivariate meta-analyses become increasingly common, further pressures are placed on reviewers to extract data in a systematic and consistent manner. Failing to do this appropriately wastes time, resources and jeopardises accuracy. This guide (data extraction for complex meta-analysis (DECiMAL)) suggests a number of points to consider when collecting data, primarily aimed at systematic reviewers preparing data for meta-analysis. Network meta-analysis (NMA), multiple outcomes analysis and analysis combining different types of data are considered in a manner that can be useful across a range of data collection programmes. The guide has been shown to be both easy to learn and useful in a small pilot study.

The Effect of Mindfulness-Based Therapy on Symptoms of Anxiety and Depression in Adult Cancer Patients and Survivors: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Piet, Jacob; Wurtzen, Hanne; Zachariae, Robert

2012-01-01

Objective: The use of mindfulness-based therapy (MBT) in oncology settings has become increasingly popular, and research in the field has rapidly expanded. The objective was by means of a systematic review and meta-analysis to evaluate the current evidence for the effect of MBT on symptoms of anxiety and depression in adult cancer patients and…

No Clear Evidence of the Effect of Cantilevered Implant Supported Fixed Restorations on the Marginal Bone or the Prosthetic Complications.

PubMed

Radi, Iman Abd-Elwahab

2016-03-01

Effect of cantilevers for implant-supported prostheses on marginal bone loss and prosthetic complications: systematic review and meta-analysis. Torrecillas-Martinez L, Monje A, Lin G, Suarez F, Ortega-Oller I, Galindo-Moreno P, Wang H. Int J Oral Maxillofac Implants 2014;29(6):1315-21. Not reported Systematic review and meta-analysis. Copyright © 2016 Elsevier Inc. All rights reserved.

[Preliminarily application of content analysis to qualitative nursing data].

PubMed

Liang, Shu-Yuan; Chuang, Yeu-Hui; Wu, Shu-Fang

2012-10-01

Content analysis is a methodology for objectively and systematically studying the content of communication in various formats. Content analysis in nursing research and nursing education is called qualitative content analysis. Qualitative content analysis is frequently applied to nursing research, as it allows researchers to determine categories inductively and deductively. This article examines qualitative content analysis in nursing research from theoretical and practical perspectives. We first describe how content analysis concepts such as unit of analysis, meaning unit, code, category, and theme are used. Next, we describe the basic steps involved in using content analysis, including data preparation, data familiarization, analysis unit identification, creating tentative coding categories, category refinement, and establishing category integrity. Finally, this paper introduces the concept of content analysis rigor, including dependability, confirmability, credibility, and transferability. This article elucidates the content analysis method in order to help professionals conduct systematic research that generates data that are informative and useful in practical application.

How mental health nurses improve their critical thinking through problem-based learning.

PubMed

Hung, Tsui-Mei; Tang, Lee-Chun; Ko, Chen-Ju

2015-01-01

Critical thinking has been regarded as one of the most important elements for nurses to improve quality of patient care. The aim of this study was to use problem-based learning (PBL) as a method in a continuing education program to evaluate nurses' critical thinking skills. A quasiexperimental study design was carried out. The "Critical Thinking Disposition Inventory" in Chinese was used for data collection. The results indicated significant improvement after PBL continuous education, notably in the dimensions of systematic analysis and curiosity. Content analysis extracted four themes: (a) changes in linear thinking required, (b) logical and systematic thinking required performance improved, (3) integration of prior knowledge and clinical application, and (4) brainstorming learning strategy. The study supports PBL as a continuing education strategy for mental health nurses, and that systematic analysis and curiosity effectively facilitate the development of critical thinking.

Early Rehabilitation in Elderly after Arthroplasty versus Internal Fixation for Unstable Intertrochanteric Fractures of Femur: Systematic Review and Meta-Analysis.

PubMed

Yoo, Jun Il; Ha, Yong Chan; Lim, Jae Young; Kang, Hyun; Yoon, Byung Ho; Kim, Hyunho

2017-05-01

The purpose of this study was to compare the outcomes focusing on the functional outcome and clinical results of replacement arthroplasty (AP) vs. internal fixation (IF) for the treatment of unstable intertrochanteric femoral fracture in elderly. Systematic review and meta-analysis were performed on 10 available clinical studies (2 randomized controlled trials and 8 comparative studies). Subgroup analysis was performed by type of methodological quality. Partial weight bearing time in AP group was earlier than that in IF group (SMD = -0.86; 95% CI = -0.42, 1.29; P = 0.050). The overall outcomes such as mortality, reoperation rate, and complication showed no significant diffrence between the 2 groups (AP vs. IF). Therefore, this systematic review demonstrates that AP provides superior functional outcomes especially earlier mobilization, as compared to IF in elderly patients with an unstable intertrochanteric femoral fracture. © 2017 The Korean Academy of Medical Sciences.

Functional Analysis of Problem Behavior: A Systematic Approach for Identifying Idiosyncratic Variables

PubMed Central

Roscoe, Eileen M.; Schlichenmeyer, Kevin J.; Dube, William V.

2015-01-01

When inconclusive functional analysis (FA) outcomes occur, a number of modifications have been made to enhance the putative establishing operation or consequence associated with behavioral maintenance. However, a systematic method for identifying relevant events to test during modified FAs has not been evaluated. The purpose of this study was to develop and evaluate a technology for systematically identifying events to test in a modified FA after an initial FA led to inconclusive outcomes. Six individuals whose initial FA showed little or no responding or high levels only in the control condition participated. An indirect assessment (IA) questionnaire developed for identifying idiosyncratic variables was administered, and a descriptive analysis (DA) was conducted. Results from the IA only or a combination of the IA and DA were used to inform modified FA test and control conditions. Conclusive FA outcomes were obtained with five of the six participants during the modified FA phase. PMID:25930176

Qualitative fusion technique based on information poor system and its application to factor analysis for vibration of rolling bearings

NASA Astrophysics Data System (ADS)

Xia, Xintao; Wang, Zhongyu

2008-10-01

For some methods of stability analysis of a system using statistics, it is difficult to resolve the problems of unknown probability distribution and small sample. Therefore, a novel method is proposed in this paper to resolve these problems. This method is independent of probability distribution, and is useful for small sample systems. After rearrangement of the original data series, the order difference and two polynomial membership functions are introduced to estimate the true value, the lower bound and the supper bound of the system using fuzzy-set theory. Then empirical distribution function is investigated to ensure confidence level above 95%, and the degree of similarity is presented to evaluate stability of the system. Cases of computer simulation investigate stable systems with various probability distribution, unstable systems with linear systematic errors and periodic systematic errors and some mixed systems. The method of analysis for systematic stability is approved.

Follicular flushing during oocyte retrieval: a systematic review and meta-analysis.

PubMed

Roque, Matheus; Sampaio, Marcos; Geber, Selmo

2012-11-01

The purpose of this systematic review and meta-analysis was to examine the literature and identify randomized controlled trials (RCTs), in order to answer if performing follicular flushing during the oocyte retrieval may improve the assisted reproductive technologies (ART) outcomes. An exhaustive electronic search was performed using MEDLINE and EMBASE databases. Only RCTs comparing follicular flushing to aspiration only during ART, were included. We included 5 trials, with a total of 482 patients randomized, with median ages ranging from 30.5 to 37.1. The data analyses did not show significant differences regarding live birth rate, clinical pregnancies rates, and the number of oocytes retrieved. The duration of oocyte retrieval was significantly increased in the follicular flushing group. The results from this systematic review and meta-analysis suggest that there is no advantage to use of routine follicular flushing during OR in an unselected group of patients.

Nitrate supplementation improves physical performance specifically in non-athletes during prolonged open-ended tests: a systematic review and meta-analysis.

PubMed

Campos, Helton O; Drummond, Lucas R; Rodrigues, Quezia T; Machado, Frederico S M; Pires, Washington; Wanner, Samuel P; Coimbra, Cândido C

2018-03-01

Nitrate (NO3 -) is an ergogenic nutritional supplement that is widely used to improve physical performance. However, the effectiveness of NO3 - supplementation has not been systematically investigated in individuals with different physical fitness levels. The present study analysed whether different fitness levels (non-athletes v. athletes or classification of performance levels), duration of the test used to measure performance (short v. long duration) and the test protocol (time trials v. open-ended tests v. graded-exercise tests) influence the effects of NO3 - supplementation on performance. This systematic review and meta-analysis was conducted and reported according to the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. A systematic search of electronic databases, including PubMed, Web of Science, SPORTDiscus and ProQuest, was performed in August 2017. On the basis of the search and inclusion criteria, fifty-four and fifty-three placebo-controlled studies evaluating the effects of NO3 - supplementation on performance in humans were included in the systematic review and meta-analysis, respectively. NO3 - supplementation was ergogenic in non-athletes (mean effect size (ES) 0·25; 95 % CI 0·11, 0·38), particularly in evaluations of performance using long-duration open-ended tests (ES 0·47; 95 % CI 0·23, 0·71). In contrast, NO3 - supplementation did not enhance the performance of athletes (ES 0·04; 95 % CI -0·05, 0·15). After objectively classifying the participants into different performance levels, the frequency of trials showing ergogenic effects in individuals classified at lower levels was higher than that in individuals classified at higher levels. Thus, the present study indicates that dietary NO3 - supplementation improves physical performance in non-athletes, particularly during long-duration open-ended tests.

Can Cranberries Contribute to Reduce the Incidence of Urinary Tract Infections? A Systematic Review with Meta-Analysis and Trial Sequential Analysis of Clinical Trials.

PubMed

Luís, Ângelo; Domingues, Fernanda; Pereira, Luísa

2017-09-01

We sought to clarify the association between cranberry intake and the prevention of urinary tract infections. This systematic review, which complies with the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) statement, was done as a meta-analysis and trial sequential analysis of clinical trials. The findings clearly showed the potential use of cranberries for the clinical condition of urinary tract infection. Cranberry products significantly reduced the incidence of urinary tract infections as indicated by the weighted risk ratio (0.6750, 95% CI 0.5516-0.7965, p <0.0001). The results of subgroup analysis demonstrated that patients at some risk for urinary tract infections were more susceptible to the effects of cranberry ingestion. The results of the current study could be used by physicians to recommend cranberry ingestion to decrease the incidence of urinary tract infections, particularly in individuals with recurrent urinary tract infections. This would also reduce the administration of antibiotics, which could be beneficial since antibiotics can lead to the worldwide emergence of antibiotic resistant microorganisms. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

[Efficacy of racecadotril vs. smectite, probiotics or zinc as an integral part of treatment of acute diarrhea in children under five years: A meta-analysis of multiple treatments].

PubMed

Gutiérrez-Castrellón, Pedro; Ortíz-Hernández, Anna Alejandra; Llamosas-Gallardo, Beatriz; Acosta-Bastidas, Mario A; Jiménez-Gutiérrez, Carlos; Diaz-García, Luisa; Anzo-Osorio, Anahí; Estevez-Jiménez, Juliana; Jiménez-Escobar, Irma; Vidal-Vázquez, Rosa Patricia

2015-01-01

Despite major advances in treatment, acute diarrhea continues to be a public health problem in children under five years. There is no systematic approach to treatment and most evidence is assembled comparing active treatment vs. placebo. Systematic review of evidence on efficacy of adjuvants for treatment of acute diarrhea through a network meta-analysis. A systematic search of multiple databases searching clinical trials related to the use of racecadotril, smectite, Lactobacillus GG, Lactobacillus reuteri, Saccharomyces boulardii and zinc as adjuvants in acute diarrhea was done. The primary endpoint was duration of diarrhea. Information is displayed through network meta-analysis.The superiority of each coadjutant was analyzed by Sucra approach. Network meta-analysis showed race cadotril was better when compared with placebo and other adjuvants. Sucra analysis showed racecadotril as the first option followed by smectite and Lactobacillus reuteri. Considering a strategic decision making approach, network meta-analysis allows us to establish the therapeutic superiority of racecadotril as an adjunct for the comprehensive management of acute diarrhea in children aged less than five years.

Does Consideration and Assessment of Effects on Health Equity Affect the Conclusions of Systematic Reviews? A Methodology Study

PubMed Central

Welch, Vivian; Petticrew, Mark; Ueffing, Erin; Benkhalti Jandu, Maria; Brand, Kevin; Dhaliwal, Bharbhoor; Kristjansson, Elizabeth; Smylie, Janet; Wells, George Anthony; Tugwell, Peter

2012-01-01

Introduction Tackling health inequities both within and between countries remains high on the agenda of international organizations including the World Health Organization and local, regional and national governments. Systematic reviews can be a useful tool to assess effects on equity in health status because they include studies conducted in a variety of settings and populations. This study aims to describe the extent to which the impacts of health interventions on equity in health status are considered in systematic reviews, describe methods used, and assess the implications of their equity related findings for policy, practice and research. Methods We conducted a methodology study of equity assessment in systematic reviews. Two independent reviewers extracted information on the reporting and analysis of impacts of health interventions on equity in health status in a group of 300 systematic reviews collected from all systematic reviews indexed in one month of MEDLINE, using a pre-tested data collection form. Any differences in data extraction were resolved by discussion. Results Of the 300 systematic reviews, 224 assessed the effectiveness of interventions on health outcomes. Of these 224 reviews, 29 systematic reviews assessed effects on equity in health status using subgroup analysis or targeted analyses of vulnerable populations. Of these, seven conducted subgroup analyses related to health equity which were reported in insufficient detail to judge their credibility. Of these 29 reviews, 18 described implications for policy and practice based on assessment of effects on health equity. Conclusion The quality and completeness of reporting should be enhanced as a priority, because without this policymakers and practitioners will continue lack the evidence base they need to inform decision-making about health inequity. Furthermore, there is a need to develop methods to systematically consider impacts on equity in health status that is currently lacking in systematic reviews. PMID:22427804

Content analysis of advertisements related to oral health in children: a systematic review and meta-analysis.

PubMed

Pournaghi Azar, F; Mamizadeh, M; Nikniaz, Z; Ghojazadeh, M; Hajebrahimi, S; Salehnia, F; Mashhadi Abdolahi, H

2018-03-01

The evidence about the content of TV advertisements broadcast during children's viewing times with an emphasis on the number of food advertisements and the number of cariogenic food advertisements was systematically reviewed and meta-analyzed. A systematic review and meta-analysis. Articles published up until October 2017 in PubMed, Scopus, Embase, Web of Science, Cochrane Library, and Persian databases such as Magiran, IranDoc, and Iranmedex with the keywords that were related to advertising and oral health in children were searched and screened by two reviewers independently, and the outcomes of interest were extracted. Meta-analysis was performed using the Comprehensive Meta-Analysis, version 2.0. A total of 480 titles were retrieved and reduced to 256 eligible studies after deletion of duplicates, and finally, after closer assessment of titles and abstracts, five articles were selected for systematic review and meta-analysis. Of the included studies, three were conducted in the UK, one in India, and one in Greece. About 38.0% (95% confidence interval: 19.6-60.6, P = 0.296) of advertisements were related to food and also about 70.6% (95% confidence interval: 53.7-83.3, P < 0.019) of food advertisements were related to cariogenic foods. Food advertising during children's programs is dominated by food items that are potentially harmful to oral health. Moreover, the advertisements shifted toward food items that appeared healthy but contain a large amount of hidden sugar. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Measuring The cmb Polarization At 94 GHz With The QUIET Pseudo-cL Pipeline

NASA Astrophysics Data System (ADS)

Buder, Immanuel; QUIET Collaboration

2012-01-01

The Q/U Imaging ExperimenT (QUIET) aims to limit or detect cosmic microwave background (CMB) B-mode polarization from inflation. This talk is part of a 3-talk series on QUIET. The previous talk describes the QUIET science and instrument. QUIET has two parallel analysis pipelines which are part of an effort to validate the analysis and confirm the result. In this talk, I will describe the analysis methods of one of these: the pseudo-Cl pipeline. Calibration, noise modeling, filtering, and data-selection choices are made following a blind-analysis strategy. Central to this strategy is a suite of 30 null tests, each motivated by a possible instrumental problem or systematic effect. The systematic errors are also evaluated through full-season simulations in the blind stage of the analysis before the result is known. The CMB power spectra are calculated using a pseudo-Cl cross-correlation technique which suppresses contamination and makes the result insensitive to noise bias. QUIET will detect the first three peaks of the even-parity (E-mode) spectrum at high significance. I will show forecasts of the systematic errors for these results and for the upper limit on B-mode polarization. The very low systematic errors in these forecasts show that the technology is ready to be applied in a more sensitive next-generation experiment. The next and final talk in this series covers the other parallel analysis pipeline, based on maximum likelihood methods. This work was supported by NSF and the Department of Education.

Screening strategies for atrial fibrillation: a systematic review and cost-effectiveness analysis.

PubMed

Welton, Nicky J; McAleenan, Alexandra; Thom, Howard Hz; Davies, Philippa; Hollingworth, Will; Higgins, Julian Pt; Okoli, George; Sterne, Jonathan Ac; Feder, Gene; Eaton, Diane; Hingorani, Aroon; Fawsitt, Christopher; Lobban, Trudie; Bryden, Peter; Richards, Alison; Sofat, Reecha

2017-05-01

Atrial fibrillation (AF) is a common cardiac arrhythmia that increases the risk of thromboembolic events. Anticoagulation therapy to prevent AF-related stroke has been shown to be cost-effective. A national screening programme for AF may prevent AF-related events, but would involve a substantial investment of NHS resources. To conduct a systematic review of the diagnostic test accuracy (DTA) of screening tests for AF, update a systematic review of comparative studies evaluating screening strategies for AF, develop an economic model to compare the cost-effectiveness of different screening strategies and review observational studies of AF screening to provide inputs to the model. Systematic review, meta-analysis and cost-effectiveness analysis. Primary care. Adults. Screening strategies, defined by screening test, age at initial and final screens, screening interval and format of screening {systematic opportunistic screening [individuals offered screening if they consult with their general practitioner (GP)] or systematic population screening (when all eligible individuals are invited to screening)}. Sensitivity, specificity and diagnostic odds ratios; the odds ratio of detecting new AF cases compared with no screening; and the mean incremental net benefit compared with no screening. Two reviewers screened the search results, extracted data and assessed the risk of bias. A DTA meta-analysis was perfomed, and a decision tree and Markov model was used to evaluate the cost-effectiveness of the screening strategies. Diagnostic test accuracy depended on the screening test and how it was interpreted. In general, the screening tests identified in our review had high sensitivity (> 0.9). Systematic population and systematic opportunistic screening strategies were found to be similarly effective, with an estimated 170 individuals needed to be screened to detect one additional AF case compared with no screening. Systematic opportunistic screening was more likely to be cost-effective than systematic population screening, as long as the uptake of opportunistic screening observed in randomised controlled trials translates to practice. Modified blood pressure monitors, photoplethysmography or nurse pulse palpation were more likely to be cost-effective than other screening tests. A screening strategy with an initial screening age of 65 years and repeated screens every 5 years until age 80 years was likely to be cost-effective, provided that compliance with treatment does not decline with increasing age. A national screening programme for AF is likely to represent a cost-effective use of resources. Systematic opportunistic screening is more likely to be cost-effective than systematic population screening. Nurse pulse palpation or modified blood pressure monitors would be appropriate screening tests, with confirmation by diagnostic 12-lead electrocardiography interpreted by a trained GP, with referral to a specialist in the case of an unclear diagnosis. Implementation strategies to operationalise uptake of systematic opportunistic screening in primary care should accompany any screening recommendations. Many inputs for the economic model relied on a single trial [the Screening for Atrial Fibrillation in the Elderly (SAFE) study] and DTA results were based on a few studies at high risk of bias/of low applicability. Comparative studies measuring long-term outcomes of screening strategies and DTA studies for new, emerging technologies and to replicate the results for photoplethysmography and GP interpretation of 12-lead electrocardiography in a screening population. This study is registered as PROSPERO CRD42014013739. The National Institute for Health Research Health Technology Assessment programme.

Fetuin-A levels and risk of type 2 diabetes mellitus: a systematic review and meta-analysis.

PubMed

Guo, Vivian Yawei; Cao, Bing; Cai, Chunyan; Cheng, Kenneth King-Yip; Cheung, Bernard Man Yung

2018-01-01

Fetuin-A has been linked to insulin resistance and obesity. Its role in the pathogenesis of type 2 diabetes (T2DM) has also been discussed. We aimed to investigate the prospective association of fetuin-A and the risk of T2DM in a systematic review and meta-analysis. A systematic search of studies from the MEDLINE, EMBASE, Pubmed and Web of Science using fetuin-A, diabetes and various synonyms was conducted up to June 5, 2017. Relevant studies were extracted by two reviewers independently. The quality of studies was assessed using Newcastle-Ottawa scales. Overall estimates were pooled using fixed effect with inverse variance meta-analysis. Subgroup analyses by gender, study population, techniques of assessing fetuin-A, diabetes ascertainment methods, follow-up duration and measures of association were conducted. Seven studies comprising a total of 11,497 individuals and 2176 cases of T2DM were included in the systematic review and meta-analysis. Overall, one SD increment of fetuin-A level was associated with a 23% greater risk of incident T2DM (RR: 1.23, 95% CI 1.16-1.31). No significant heterogeneity or publication bias was found. The association was relatively stable across different subgroups. However, the association seemed only evident in women, but not in men. Higher circulating fetuin-A levels were associated with increased risk of T2DM. However, the causality deserved further analysis.

Mapping vulnerability to bipolar disorder: a systematic review and meta-analysis of neuroimaging studies

PubMed Central

Fusar-Poli, Paolo; Howes, Oliver; Bechdolf, Andreas; Borgwardt, Stefan

2012-01-01

Background Although early interventions in individuals with bipolar disorder may reduce the associated personal and economic burden, the neurobiologic markers of enhanced risk are unknown. Methods Neuroimaging studies involving individuals at enhanced genetic risk for bipolar disorder (HR) were included in a systematic review. We then performed a region of interest (ROI) analysis and a whole-brain meta-analysis combined with a formal effect-sizes meta-analysis in a subset of studies. Results There were 37 studies included in our systematic review. The overall sample for the systematic review included 1258 controls and 996 HR individuals. No significant differences were detected between HR individuals and controls in the selected ROIs: striatum, amygdala, hippocampus, pituitary and frontal lobe. The HR group showed increased grey matter volume compared with patients with established bipolar disorder. The HR individuals showed increased neural response in the left superior frontal gyrus, medial frontal gyrus and left insula compared with controls, independent from the functional magnetic resonance imaging task used. There were no publication biases. Sensitivity analysis confirmed the robustness of these results. Limitations As the included studies were cross-sectional, it remains to be determined whether the observed neurofunctional and structural alterations represent risk factors that can be clinically used in preventive interventions for prodromal bipolar disorder. Conclusion Accumulating structural and functional imaging evidence supports the existence of neurobiologic trait abnormalities in individuals at genetic risk for bipolar disorder at various scales of investigation. PMID:22297067

Non-resurfacing techniques in the management of the patella at total knee arthroplasty: A systematic review and meta-analysis.

PubMed

Findlay, I; Wong, F; Smith, C; Back, D; Davies, A; Ajuied, A

2016-03-01

Recent meta-analyses support not resurfacing the patella at the time of TKA. Several different modes of intervention are reported for non-resurfacing management of the patella at TKA. We have conducted a systematic review and meta-analysis of non-resurfacing interventions in TKA. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) study methodology and reporting system was adopted, utilising the PRISMA checklist and statement. Classes of patella interventions were defined as: 0. No intervention. 1. Osteophyte excision only. 2. Osteophyte excision, denervation, with soft tissue debridement. 3. Osteophyte excision, denervation, soft tissue debridement, and drilling or micro-fracture of eburnated bone. 4. Patellar resurfacing. A meta-analysis was conducted upon the pre- and post-operative KSS for each technique. Four hundred and twenty-three studies were identified, 12 studies met the inclusion criteria for the systematic review and eight for the meta-analysis. Two studies compared different non-resurfacing patellar techniques, the other studies used the non-resurfacing cohort as controls for their prospective RCTs comparing patellar resurfacing with non-resurfacing. The meta-analysis revealed no significant difference between the techniques. We conclude that there is no significant difference in KSS for differing non-resurfacing patellar techniques, but further trials using patellofemoral specific scores may better demonstrate superior efficacy of specific classes of patella intervention, by virtue of greater sensitivity for patellofemoral pain and dysfunction. I. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Psychosocial Interventions for Depressive and Anxiety Symptoms in Individuals with Chronic Kidney Disease: Systematic Review and Meta-Analysis

PubMed Central

Pascoe, Michaela C.; Thompson, David R.; Castle, David J.; McEvedy, Samantha M.; Ski, Chantal F.

2017-01-01

Purpose: Depressive and anxiety symptoms are common amongst individuals with chronic kidney disease and are known to affect quality of life adversely. Psychosocial interventions have been shown to decrease depressive and anxiety symptoms in various chronic diseases, but few studies have examined their efficacy in people with chronic kidney disease and no meta-analysis has been published. Thus, the aim of the present systematic review and meta-analysis was to evaluate the effects of psychosocial interventions on depressive and anxiety symptoms as well as quality of life in individuals diagnosed with chronic kidney disease and/or their carers. Methods: In this systematic review and meta-analysis, we included published randomized controlled trials comparing psychosocial interventions versus usual care for impacting depressive and anxiety symptoms and quality of life. Results: Eight studies were included in the systematic review and six of these were subjected to meta-analysis. Psychosocial interventions were associated with a medium effect size for reduction in depressive symptoms and a small effect size for improved quality of life in the in individuals with chronic-kidney-disease and their carers. Some evidence suggested a reduction in anxiety. Conclusion: Psychosocial interventions appear to reduce depressive symptoms and improve quality of life in patients with chronic-kidney-disease and their carers and to have some beneficial impact on anxiety. However, the small number of identified studies indicates a need for further research in this field. PMID:28659852

Commonality and Variability Analysis for Xenon Family of Separation Virtual Machine Monitors (CVAX)

DTIC Science & Technology

2017-07-18

technical approach is a systematic application of Software Product Line Engineering (SPLE). A systematic application requires describing the family and... engineering Software family September 2016 – October 2016 OSD/OUSD/ATL/ASD(R&E)/RDOffice of Information Systems & Cyber Security RD / ASD(R&E) / AT&L...by the evolving open-source Xen hypervisor. The technical approach is a systematic application of Software Product Line Engineering (SPLE). A

A SYSTEMATIC PROCEDURE FOR DESIGNING PROCESSES WITH MULTIPLE ENVIRONMENTAL OBJECTIVES

EPA Science Inventory

Evaluation and analysis of multiple objectives are very important in designing environmentally benign processes. They require a systematic procedure for solving multi-objective decision-making problems due to the complex nature of the problems and the need for complex assessment....

An evidence-based systematic review of gymnema (Gymnema sylvestre R. Br.) by the Natural Standard Research Collaboration.

PubMed

Ulbricht, Catherine; Abrams, Tracee Rae; Basch, Ethan; Davies-Heerema, Theresa; Foppa, Ivo; Hammerness, Paul; Rusie, Erica; Tanguay-Colucci, Shaina; Taylor, Sarah; Ulbricht, Catherine; Varghese, Minney; Weissner, Wendy; Woods, Jen

2011-09-01

An evidence-based systematic review of gymnema (Gymnema sylvestre R. Br.), including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

A low proportion of systematic reviews in physical therapy are registered: a survey of 150 published systematic reviews.

PubMed

Oliveira, Crystian B; Elkins, Mark R; Lemes, Ítalo Ribeiro; de Oliveira Silva, Danilo; Briani, Ronaldo V; Monteiro, Henrique Luiz; Azevedo, Fábio Mícolis de; Pinto, Rafael Zambelli

Systematic reviews provide the best evidence about the effectiveness of healthcare interventions. Although systematic reviews are conducted with explicit and transparent methods, discrepancies might occur between the protocol and the publication. To estimate the proportion of systematic reviews of physical therapy interventions that are registered, the methodological quality of (un)registered systematic reviews and the prevalence of outcome reporting bias in registered systematic reviews. A random sample of 150 systematic reviews published in 2015 indexed on the PEDro database. We included systematic reviews written in English, Italian, Portuguese and Spanish. A checklist for assessing the methodological quality of systematic reviews tool was used. Relative risk was calculated to explore the association between meta-analysis results and the changes in the outcomes. Twenty-nine (19%) systematic reviews were registered. Funding and publication in a journal with an impact factor higher than 5.0 were associated with registration. Registered systematic reviews demonstrated significantly higher methodological quality (median=8) than unregistered systematic reviews (median=5). Nine (31%) registered systematic reviews demonstrated discrepancies between protocol and publication with no evidence that such discrepancies were applied to favor the statistical significance of the intervention (RR=1.16; 95% CI: 0.63-2.12). A low proportion of systematic reviews in the physical therapy field are registered. The registered systematic reviews showed high methodological quality without evidence of outcome reporting bias. Further strategies should be implemented to encourage registration. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

Impact of point-of-care diagnostics on maternal outcomes in HIV-infected women: systematic review and meta-analysis protocol

PubMed Central

Mashamba-Thompson, T P; Sartorius, B; Thabane, L; Shi, C X; Drain, P K

2016-01-01

Introduction Studies indicate substandard diagnostic care, delayed and missed diagnosis as some of the contributing factors to maternal mortality. The clinical impact of point-of-care (POC) diagnostics has been shown in the monitoring and treatment of a variety of infectious diseases, including HIV/AIDS and tuberculosis. The objective of this systematic review is to investigate the impact of POC diagnostics on maternal outcomes for HIV-infected women. Methods We will conduct a systematic review to evaluate the impact of POC diagnostics for improving desired healthcare outcomes for HIV-infected women. The search strategy will involve electronic databases including: Cochrane Infectious Disease Group Specialised Register; Cochrane Central Register of Control Trials, published in The Cochrane Library; PubMed; EBSCOhost and LILACS. The studies will be mapped in 2 stages: stage 1 will map studies descriptively by focus and method; stage 2 will involve additional inclusion criteria, quality assessment and data extraction undertaken by 2 reviewers in parallel. Evidence will be synthesised using relevant systematic research tools: meta-analysis and subgroup analysis will be conducted using RevMan and Stata 13 will be used for meta-regressions. We will follow recommendations described in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and the Cochrane Handbook for Intervention Reviews. Ethics and dissemination We anticipate finding a large number of studies on POC diagnostic interventions on maternal outcomes in HIV-infected women, which, once summarised, will be useful to guide future diagnostic interventions. The protocol for the systematic review has been registered in PROSPERO. The study will be disseminated electronically and in print. It will also be presented to conferences related to HIV/AIDS, POC diagnostics and maternal health. Trial registration number PROSPERO CRD42014015439. PMID:26817633

Is there a social gradient of sarcopenia? A meta-analysis and systematic review protocol.

PubMed

Green, Darci; Duque, Gustavo; Fredman, Nick; Rizvi, Aoun; Brennan-Olsen, Sharon Lee

2018-01-13

Sarcopenia (or loss of muscle mass and function) is a relatively new area within the field of musculoskeletal research and medicine. Investigating whether there is a social gradient, including occupation type and income level, of sarcopenia, as observed for other diseases, will contribute significantly to the limited evidence base for this disease. This new information may inform the prevention and management of sarcopenia and widen the evidence base to support existing and future health campaigns. We will conduct a systematic search of the databases PubMed, Ovid, CINAHL, Scopus and EMBASE to identify articles that investigate associations between social determinants of health and sarcopenia in adults aged 50 years and older. Eligibility of the selected studies will be determined by two independent reviewers. The methodological quality of eligible studies will be assessed according to predetermined criteria. Established statistical methods to identify and control for heterogeneity will be used, and where appropriate, we will conduct a meta-analysis. In the event that heterogeneity prevents numerical synthesis, a best evidence analysis will be employed. This systematic review protocol adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols reporting guidelines and will be registered with the International Prospective Register of Systematic Reviews (PROSPERO). This systematic review will use published data, thus ethical permissions will not be required. In addition to peer-reviewed publication, our results will be presented at (inter)national conferences relevant to the field of sarcopenia, ageing and/or musculoskeletal health and disseminated both electronically and in print. CRD42017072253. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Early repositioning through compound set enrichment analysis: a knowledge-recycling strategy.

PubMed

Temesi, Gergely; Bolgár, Bence; Arany, Adám; Szalai, Csaba; Antal, Péter; Mátyus, Péter

2014-04-01

Despite famous serendipitous drug repositioning success stories, systematic projects have not yet delivered the expected results. However, repositioning technologies are gaining ground in different phases of routine drug development, together with new adaptive strategies. We demonstrate the power of the compound information pool, the ever-growing heterogeneous information repertoire of approved drugs and candidates as an invaluable catalyzer in this transition. Systematic, computational utilization of this information pool for candidates in early phases is an open research problem; we propose a novel application of the enrichment analysis statistical framework for fusion of this information pool, specifically for the prediction of indications. Pharmaceutical consequences are formulated for a systematic and continuous knowledge recycling strategy, utilizing this information pool throughout the drug-discovery pipeline.

Hyaluronic acid injection therapy for osteoarthritis of the knee: concordant efficacy and conflicting serious adverse events in two systematic reviews.

PubMed

O'Hanlon, Claire E; Newberry, Sydne J; Booth, Marika; Grant, Sean; Motala, Aneesa; Maglione, Margaret A; FitzGerald, John D; Shekelle, Paul G

2016-11-04

The prevalence of knee osteoarthritis (OA)/degenerative joint disease (DJD) is increasing in the USA. Systematic reviews of treatment efficacy and adverse events (AEs) of hyaluronic acid (HA) injections report conflicting evidence about the balance of benefits and harms. We review evidence on efficacy and AEs of intraarticular viscosupplementation with HA in older individuals with knee osteoarthritis and account for differences in these conclusions from another systematic review. We searched PubMed and eight other databases and gray literature sources from 1990 to December 12, 2014. Double-blind placebo-controlled randomized controlled trials (RCTs) reporting functional outcomes or quality-of-life; RCTs and observational studies on delay/avoidance of arthroplasty; RCTs, case reports, and large cohort studies and case series assessing safety; and systematic reviews reporting on knee pain were considered for inclusion. A standardized, pre-defined protocol was applied by two independent reviewers to screen titles and abstracts, review full text, and extract details on study design, interventions, outcomes, and quality. We compared our results with those of a prior systematic review and found them to be discrepant; our analysis of why this discrepancy occurred is the focus of this manuscript. Eighteen RCTs reported functional outcomes: pooled analysis of ten placebo-controlled, blinded trials showed a standardized mean difference of -0.23 (95 % confidence interval (CI) -0.45 to -0.01) favoring HA at 6 months. Studies reported few serious adverse events (SAEs) and no significant differences in non-serious adverse events (NSAEs) (relative risk (RR) [95 % CI] 1.03 [0.93-1.15] or SAEs (RR [95 % CI] 1.39 [0.78-2.47]). A recent prior systematic review reported similar functional outcomes, but significant SAE risk. Differences in SAE inclusion and synthesis accounted for the disparate conclusions. Trials show a small but significant effect of HA on function on which recent systematic reviews agree, but lack of AE synthesis standardization leads to opposite conclusions about the balance of benefits and harms. A limitation of the re-analysis of the prior systematic review is that it required imputation of missing data.

The Efficacy of Guanxinning Injection in Treating Angina Pectoris: Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Jia, Yongliang; Leung, Siu-wai; Lee, Ming-Yuen; Cui, Guozhen; Huang, Xiaohui; Pan, Fongha

2013-01-01

Objective. The randomized controlled trials (RCTs) on Guanxinning injection (GXN) in treating angina pectoris were published only in Chinese and have not been systematically reviewed. This study aims to provide a PRISMA-compliant and internationally accessible systematic review to evaluate the efficacy of GXN in treating angina pectoris. Methods. The RCTs were included according to prespecified eligibility criteria. Meta-analysis was performed to evaluate the symptomatic (SYMPTOMS) and electrocardiographic (ECG) improvements after treatment. Odds ratios (ORs) were used to measure effect sizes. Subgroup analysis, sensitivity analysis, and metaregression were conducted to evaluate the robustness of the results. Results. Sixty-five RCTs published between 2002 and 2012 with 6064 participants were included. Overall ORs comparing GXN with other drugs were 3.32 (95% CI: [2.72, 4.04]) in SYMPTOMS and 2.59 (95% CI: [2.14, 3.15]) in ECG. Subgroup analysis, sensitivity analysis, and metaregression found no statistically significant dependence of overall ORs upon specific study characteristics. Conclusion. This meta-analysis of eligible RCTs provides evidence that GXN is effective in treating angina pectoris. This evidence warrants further RCTs of higher quality, longer follow-up periods, larger sample sizes, and multicentres/multicountries for more extensive subgroup, sensitivity, and metaregression analyses. PMID:23634167

Poor methodological quality and reporting standards of systematic reviews in burn care management.

PubMed

Wasiak, Jason; Tyack, Zephanie; Ware, Robert; Goodwin, Nicholas; Faggion, Clovis M

2017-10-01

The methodological and reporting quality of burn-specific systematic reviews has not been established. The aim of this study was to evaluate the methodological quality of systematic reviews in burn care management. Computerised searches were performed in Ovid MEDLINE, Ovid EMBASE and The Cochrane Library through to February 2016 for systematic reviews relevant to burn care using medical subject and free-text terms such as 'burn', 'systematic review' or 'meta-analysis'. Additional studies were identified by hand-searching five discipline-specific journals. Two authors independently screened papers, extracted and evaluated methodological quality using the 11-item A Measurement Tool to Assess Systematic Reviews (AMSTAR) tool and reporting quality using the 27-item Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Characteristics of systematic reviews associated with methodological and reporting quality were identified. Descriptive statistics and linear regression identified features associated with improved methodological quality. A total of 60 systematic reviews met the inclusion criteria. Six of the 11 AMSTAR items reporting on 'a priori' design, duplicate study selection, grey literature, included/excluded studies, publication bias and conflict of interest were reported in less than 50% of the systematic reviews. Of the 27 items listed for PRISMA, 13 items reporting on introduction, methods, results and the discussion were addressed in less than 50% of systematic reviews. Multivariable analyses showed that systematic reviews associated with higher methodological or reporting quality incorporated a meta-analysis (AMSTAR regression coefficient 2.1; 95% CI: 1.1, 3.1; PRISMA regression coefficient 6·3; 95% CI: 3·8, 8·7) were published in the Cochrane library (AMSTAR regression coefficient 2·9; 95% CI: 1·6, 4·2; PRISMA regression coefficient 6·1; 95% CI: 3·1, 9·2) and included a randomised control trial (AMSTAR regression coefficient 1·4; 95%CI: 0·4, 2·4; PRISMA regression coefficient 3·4; 95% CI: 0·9, 5·8). The methodological and reporting quality of systematic reviews in burn care requires further improvement with stricter adherence by authors to the PRISMA checklist and AMSTAR tool. © 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Bias due to selective inclusion and reporting of outcomes and analyses in systematic reviews of randomised trials of healthcare interventions.

PubMed

Page, Matthew J; McKenzie, Joanne E; Kirkham, Jamie; Dwan, Kerry; Kramer, Sharon; Green, Sally; Forbes, Andrew

2014-10-01

Systematic reviews may be compromised by selective inclusion and reporting of outcomes and analyses. Selective inclusion occurs when there are multiple effect estimates in a trial report that could be included in a particular meta-analysis (e.g. from multiple measurement scales and time points) and the choice of effect estimate to include in the meta-analysis is based on the results (e.g. statistical significance, magnitude or direction of effect). Selective reporting occurs when the reporting of a subset of outcomes and analyses in the systematic review is based on the results (e.g. a protocol-defined outcome is omitted from the published systematic review). To summarise the characteristics and synthesise the results of empirical studies that have investigated the prevalence of selective inclusion or reporting in systematic reviews of randomised controlled trials (RCTs), investigated the factors (e.g. statistical significance or direction of effect) associated with the prevalence and quantified the bias. We searched the Cochrane Methodology Register (to July 2012), Ovid MEDLINE, Ovid EMBASE, Ovid PsycINFO and ISI Web of Science (each up to May 2013), and the US Agency for Healthcare Research and Quality (AHRQ) Effective Healthcare Program's Scientific Resource Center (SRC) Methods Library (to June 2013). We also searched the abstract books of the 2011 and 2012 Cochrane Colloquia and the article alerts for methodological work in research synthesis published from 2009 to 2011 and compiled in Research Synthesis Methods. We included both published and unpublished empirical studies that investigated the prevalence and factors associated with selective inclusion or reporting, or both, in systematic reviews of RCTs of healthcare interventions. We included empirical studies assessing any type of selective inclusion or reporting, such as investigations of how frequently RCT outcome data is selectively included in systematic reviews based on the results, outcomes and analyses are discrepant between protocol and published review or non-significant outcomes are partially reported in the full text or summary within systematic reviews. Two review authors independently selected empirical studies for inclusion, extracted the data and performed a risk of bias assessment. A third review author resolved any disagreements about inclusion or exclusion of empirical studies, data extraction and risk of bias. We contacted authors of included studies for additional unpublished data. Primary outcomes included overall prevalence of selective inclusion or reporting, association between selective inclusion or reporting and the statistical significance of the effect estimate, and association between selective inclusion or reporting and the direction of the effect estimate. We combined prevalence estimates and risk ratios (RRs) using a random-effects meta-analysis model. Seven studies met the inclusion criteria. No studies had investigated selective inclusion of results in systematic reviews, or discrepancies in outcomes and analyses between systematic review registry entries and published systematic reviews. Based on a meta-analysis of four studies (including 485 Cochrane Reviews), 38% (95% confidence interval (CI) 23% to 54%) of systematic reviews added, omitted, upgraded or downgraded at least one outcome between the protocol and published systematic review. The association between statistical significance and discrepant outcome reporting between protocol and published systematic review was uncertain. The meta-analytic estimate suggested an increased risk of adding or upgrading (i.e. changing a secondary outcome to primary) when the outcome was statistically significant, although the 95% CI included no association and a decreased risk as plausible estimates (RR 1.43, 95% CI 0.71 to 2.85; two studies, n = 552 meta-analyses). Also, the meta-analytic estimate suggested an increased risk of downgrading (i.e. changing a primary outcome to secondary) when the outcome was statistically significant, although the 95% CI included no association and a decreased risk as plausible estimates (RR 1.26, 95% CI 0.60 to 2.62; two studies, n = 484 meta-analyses). None of the included studies had investigated whether the association between statistical significance and adding, upgrading or downgrading of outcomes was modified by the type of comparison, direction of effect or type of outcome; or whether there is an association between direction of the effect estimate and discrepant outcome reporting.Several secondary outcomes were reported in the included studies. Two studies found that reasons for discrepant outcome reporting were infrequently reported in published systematic reviews (6% in one study and 22% in the other). One study (including 62 Cochrane Reviews) found that 32% (95% CI 21% to 45%) of systematic reviews did not report all primary outcomes in the abstract. Another study (including 64 Cochrane and 118 non-Cochrane reviews) found that statistically significant primary outcomes were more likely to be completely reported in the systematic review abstract than non-significant primary outcomes (RR 2.66, 95% CI 1.81 to 3.90). None of the studies included systematic reviews published after 2009 when reporting standards for systematic reviews (Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Statement, and Methodological Expectations of Cochrane Intervention Reviews (MECIR)) were disseminated, so the results might not be generalisable to more recent systematic reviews. Discrepant outcome reporting between the protocol and published systematic review is fairly common, although the association between statistical significance and discrepant outcome reporting is uncertain. Complete reporting of outcomes in systematic review abstracts is associated with statistical significance of the results for those outcomes. Systematic review outcomes and analysis plans should be specified prior to seeing the results of included studies to minimise post-hoc decisions that may be based on the observed results. Modifications that occur once the review has commenced, along with their justification, should be clearly reported. Effect estimates and CIs should be reported for all systematic review outcomes regardless of the results. The lack of research on selective inclusion of results in systematic reviews needs to be addressed and studies that avoid the methodological weaknesses of existing research are also needed.

Survival Rate of Delayed Implants Placed in Healed Extraction Sockets is Significantly Higher Than That of Immediate Implants Placed in Fresh Extraction Sockets.

PubMed

Antetomaso, Jordan; Kumar, Satish

2018-03-01

Immediate implant placement into fresh extraction sockets versus delayed implants into healed sockets: a systematic review and meta-analysis. Mello CC, Lemos CAA, Verri FR, Dos Santos DM, Goiato MC, Pellizzer EP. Int J Oral Maxillofac Surg 2017; 46(9):1162-77. None TYPE OF STUDY/DESIGN: Systematic review with meta-analysis of data. Copyright © 2017 Elsevier Inc. All rights reserved.

Outcomes of Robotic Sacrocolpopexy: A Systematic Review and Meta-analysis

PubMed Central

Hudson, Catherine O.; Northington, Gina M.; Lyles, Robert H.; Karp, Deborah R.

2015-01-01

Objectives Robotic sacrocolpopexy has been rapidly incorporated into surgical practice without comprehensive and systematically published outcome data. The aim of this study was to systematically review the current published peer-reviewed literature on robotic-assisted laparoscopic sacrocolpopexy with greater than six-month anatomic outcome data. Methods Studies were selected after applying predetermined inclusion and exclusion criteria to a MEDLINE search. Two independent reviewers blinded to each other’s results abstracted demographic data, perioperative information and postoperative outcomes. The primary outcome assessed was anatomic success rate defined as ≤POP-Q Stage 1. A random effects model was performed for meta-analysis of selected outcomes. Results 13 studies were selected for the systematic review. Meta-analysis yielded a combined estimated success rate of 98.6% (95%CI 97.0–100%). The combined estimated rate of mesh exposure/erosion was 4.1% (95%CI 1.4–6.9%), and the rate of reoperation for mesh revision was 1.7%. The rates of reoperation for recurrent apical and non-apical prolapse were 0.8% and 2.5% respectively. The most common surgical complication (excluding mesh erosion) was cystotomy (2.8%), followed by wound infection (2.4%). Conclusions The outcomes of this analysis indicate that robotic sacrocolpopexy is an effective surgical treatment for apical prolapse with high anatomic cure rate and low rate of complications. PMID:25181374

A meta-analysis but not a systematic review: an evaluation of the Global BMI Mortality Collaboration.

PubMed

Flegal, Katherine M; Ioannidis, John P A

2017-08-01

Meta-analyses of individual participant data (MIPDs) offer many advantages and are considered the highest level of evidence. However, MIPDs can be seriously compromised when they are not solidly founded upon a systematic review. These data-intensive collaborative projects may be led by experts who already have deep knowledge of the literature in the field and of the results of published studies and how these results vary based on different analytical approaches. If investigators tailor the searches, eligibility criteria, and analysis plan of the MIPD, they run the risk of reaching foregone conclusions. We exemplify this potential bias in a MIPD on the association of body mass index with mortality conducted by a collaboration of outstanding and extremely knowledgeable investigators. Contrary to a previous meta-analysis of group data that used a systematic review approach, the MIPD did not seem to use a formal search: it considered 239 studies, of which the senior author was previously aware of at least 238, and it violated its own listed eligibility criteria to include those studies and exclude other studies. It also preferred an analysis plan that was also known to give a specific direction of effects in already published results of most of the included evidence. MIPDs where results of constituent studies are already largely known need safeguards to their validity. These may include careful systematic searches, adherence to the Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data guidelines, and exploration of the robustness of results with different analyses. They should also avoid selective emphasis on foregone conclusions based on previously known results with specific analytical choices. Copyright © 2017 Elsevier Inc. All rights reserved.

Pharmacotherapies for fatigue in chronic liver disease (CLD): a systematic review and meta-analysis (protocol).

PubMed

Effiong, Andem; Kumari, Prerna

2018-02-14

This is the protocol for a systematic review (and meta-analysis) of an intervention. The primary objective of this systematic review will be to assess the benefits and harms of pharmacological therapies (pharmacotherapies) for the management of fatigue in adults with CLD of any etiology. The effects of pharmacological therapies on fatigue in CLD will be compared against those of placebo, no intervention, or non-pharmacological interventions. Specifically, this review will examine whether pharmacological therapies improve CLD-associated fatigue, and if they do, what key elements are associated with their effectiveness. The results of this systematic review will assist clinicians, policy-makers, researchers, and people with CLD in decision-making on how best to manage fatigue and its associated symptoms. MEDLINE, SCOPUS, EMBASE, EU Clinical Trials Register, WHO International Clinical Trials Registry Platform, CENTRAL (The Cochrane Library), ClinicalTrials.gov, reference lists of articles and conference proceedings will be searched for relevant studies. No language or date restrictions will be applied. Eligible studies will include adults with CLD of any etiology. Included studies will be randomized controlled trials. From included studies, data on participant characteristics, study design, setting, research ethics compliance, and intervention outcomes will be extracted. Risk of bias in included studies will be assessed using the Cochrane Risk of Bias Tool. A random-effects meta-analysis will be conducted. If substantial or considerable levels of heterogeneity are detected, analysis will be limited to a narrative synthesis. This systematic review will examine the effectiveness of pharmacological therapies on fatigue reduction in people with CLD. Such therapies may be more effective than non-pharmacological interventions in treating fatigue symptoms in CLD. Evidence derived from the findings of this study will guide future practice, policy, and research. PROSPERO, CRD42017076957.

Use of a problem-based learning teaching model for undergraduate medical and nursing education: a systematic review and meta-analysis

PubMed Central

Sayyah, Mehdi; Shirbandi, Kiarash; Saki-Malehi, Amal; Rahim, Fakher

2017-01-01

Objectives The aim of this systematic review and meta-analysis was to evaluate the problem-based learning (PBL) method as an alternative to conventional educational methods in Iranian undergraduate medical courses. Materials and methods We systematically searched international datasets banks, including PubMed, Scopus, and Embase, and internal resources of banks, including MagirIran, IranMedex, IranDoc, and Scientific Information Database (SID), using appropriate search terms, such as “PBL”, “problem-based learning”, “based on problems”, “active learning”, and“ learner centered”, to identify PBL studies, and these were combined with other key terms such as “medical”, “undergraduate”, “Iranian”, “Islamic Republic of Iran”, “I.R. of Iran”, and “Iran”. The search included the period from 1980 to 2016 with no language limits. Results Overall, a total of 1,057 relevant studies were initially found, of which 21 studies were included in the systematic review and meta-analysis. Of the 21 studies, 12 (57.14%) had a high methodological quality. Considering the pooled effect size data, there was a significant difference in the scores (standardized mean difference [SMD]=0.80, 95% CI [0.52, 1.08], P<0.000) in favor of PBL, compared with the lecture-based method. Subgroup analysis revealed that using PBL alone is more favorable compared to using a mixed model with other learning methods such as lecture-based learning (LBL). Conclusion The results of this systematic review showed that using PBL may have a positive effect on the academic achievement of undergraduate medical courses. The results suggest that teachers and medical education decision makers give more attention on using this method for effective and proper training. PMID:29042827

Understanding persuasion contexts in health gamification: A systematic analysis of gamified health behavior change support systems literature.

PubMed

Alahäivälä, Tuomas; Oinas-Kukkonen, Harri

2016-12-01

Gamification is increasingly used as a design strategy when developing behavior change support systems in the healthcare domain. It is commonly agreed that understanding the contextual factors is critical for successful gamification, but systematic analyses of the persuasive contexts have been lacking so far within gamified health intervention studies. Through a persuasion context analysis of the gamified health behavior change support systems (hBCSSs) literature, we inspect how the contextual factors have been addressed in the prior gamified health BCSS studies. The implications of this study are to provide the practitioners and researchers examples of how to conduct a systematic analysis to help guide the design and research on gamified health BCSSs. The ideas derived from the analysis of the included studies will help identify potential pitfalls and shortcomings in both the research and implementations of gamified health behavior change support systems. We systematically analyzed the persuasion contexts of 15 gamified health intervention studies. According to our results, gamified hBCSSs are implemented under different facets of lifestyle change and treatments compliance, and use a multitude of technologies and methods. We present a set of ideas and concepts to help improve endeavors in studying gamified health intervention through comprehensive understanding of the persuasive contextual factors. Future research on gamified hBCSSs should systematically compare the different combinations of contextual factors, related theories, chosen gamification strategies, and the study of outcomes to help understand how to achieve the most efficient use of gamification on the different aspects of healthcare. Analyzing the persuasion context is essential to achieve this. With the attained knowledge, those planning health interventions can choose the 'tried-and-tested' approaches for each particular situation, rather than develop solutions in an ad-hoc manner. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Single- versus double-row repair for full-thickness rotator cuff tears using suture anchors. A systematic review and meta-analysis of basic biomechanical studies.

PubMed

Hohmann, Erik; König, Anya; Kat, Cor-Jacques; Glatt, Vaida; Tetsworth, Kevin; Keough, Natalie

2018-07-01

The purpose of this study was to perform a systematic review and meta-analysis comparing single- and double-row biomechanical studies to evaluate load to failure, mode of failure and gap formation. A systematic review of MEDLINE, Embase, Scopus and Google Scholar was performed from 1990 through 2016. The inclusion criteria were: documentation of ultimate load to failure, failure modes and documentation of elongation or gap formation. Studies were excluded if the study protocol did not use human specimens. Publication bias was assessed by funnel plot and Egger's test. The risk of bias was established using the Cochrane Collaboration's risk of bias tool. Heterogeneity was assessed using χ 2 and I 2 statistic. Eight studies were included. The funnel plot was asymmetric suggesting publication bias, which was confirmed by Egger's test (p = 0.04). The pooled estimate for load to failure demonstrated significant differences (SMD 1.228, 95% CI: 0.55-5.226, p = 0.006, I 2  = 60.47%), favouring double-row repair. There were no differences for failure modes. The pooled estimate for elongation/gap formation demonstrated significant differences (SMD 0.783, 95% CI: 0.169-1.398, p = 0.012, I 2  = 58.8%), favouring double-row repair. The results of this systematic review and meta-analysis suggest that double-row repair is able to tolerate a significantly greater load to failure. Gap formation was also significantly lower in the double-row repair group, but both of these findings should be interpreted with caution because of the inherent interstudy heterogeneity. Systematic review and meta-analysis.

Current status of accurate prognostic awareness in advanced/terminally ill cancer patients: Systematic review and meta-regression analysis.

PubMed

Chen, Chen Hsiu; Kuo, Su Ching; Tang, Siew Tzuh

2017-05-01

No systematic meta-analysis is available on the prevalence of cancer patients' accurate prognostic awareness and differences in accurate prognostic awareness by publication year, region, assessment method, and service received. To examine the prevalence of advanced/terminal cancer patients' accurate prognostic awareness and differences in accurate prognostic awareness by publication year, region, assessment method, and service received. Systematic review and meta-analysis. MEDLINE, Embase, The Cochrane Library, CINAHL, and PsycINFO were systematically searched on accurate prognostic awareness in adult patients with advanced/terminal cancer (1990-2014). Pooled prevalences were calculated for accurate prognostic awareness by a random-effects model. Differences in weighted estimates of accurate prognostic awareness were compared by meta-regression. In total, 34 articles were retrieved for systematic review and meta-analysis. At best, only about half of advanced/terminal cancer patients accurately understood their prognosis (49.1%; 95% confidence interval: 42.7%-55.5%; range: 5.4%-85.7%). Accurate prognostic awareness was independent of service received and publication year, but highest in Australia, followed by East Asia, North America, and southern Europe and the United Kingdom (67.7%, 60.7%, 52.8%, and 36.0%, respectively; p = 0.019). Accurate prognostic awareness was higher by clinician assessment than by patient report (63.2% vs 44.5%, p < 0.001). Less than half of advanced/terminal cancer patients accurately understood their prognosis, with significant variations by region and assessment method. Healthcare professionals should thoroughly assess advanced/terminal cancer patients' preferences for prognostic information and engage them in prognostic discussion early in the cancer trajectory, thus facilitating their accurate prognostic awareness and the quality of end-of-life care decision-making.

Transcranial direct-current stimulation (tDCS) for bipolar depression: A systematic review and meta-analysis.

PubMed

Dondé, Clément; Amad, Ali; Nieto, Isabel; Brunoni, André Russowsky; Neufeld, Nicholas H; Bellivier, Frank; Poulet, Emmanuel; Geoffroy, Pierre-Alexis

2017-08-01

Bipolar disorder (BD) is a severe and recurrent brain disorder that can manifest in manic or depressive episodes. Transcranial Direct Current Stimulation (tDCS) has been proposed as a novel therapeutic modality for patients experiencing bipolar depression, for which standard treatments are often inefficient. While several studies have been conducted in this patient group, there has been no systematic review or meta-analysis that specifically examines bipolar depression. We aimed to address this gap in the literature and evaluated the efficacy and tolerability of tDCS in patients fulfilling DSM-IV-TR criteria for BD I, II, or BD not otherwise specified (NOS). We systematically searched the literature from April 2002 to November 2016 to identify relevant publications for inclusion in our systematic review and meta-analysis. Effect sizes for depression rating-scale scores were expressed as the standardized mean difference (SMD) before and after tDCS. Thirteen of 382 identified studies met eligibility criteria for our systematic review. The meta-analysis included 46 patients from 7 studies with depression rating-scale scores pre- and post-tDCS. Parameters of tDCS procedures were heterogeneous. Depression scores decreased significantly with a medium effect size after acute-phase of treatment (SMD 0.71 [0.25-1.18], z=3.00, p=0.003) and at the furthest endpoint (SMD 1.27 [0.57-1.97], z=3.57, p=0.0004). Six cases of affective switching under tDCS treatment protocols were observed. Depressive symptoms respond to tDCS in patients with BD. Additional studies, and particularly randomized controlled trials, are needed to clarify the effectiveness of tDCS in bipolar depression, the frequency of tDCS-emergent hypomania/mania, and which tDCS modalities are most efficient. Copyright © 2017 Elsevier Inc. All rights reserved.

Including mixed methods research in systematic reviews: examples from qualitative syntheses in TB and malaria control.

PubMed

Atkins, Salla; Launiala, Annika; Kagaha, Alexander; Smith, Helen

2012-04-30

Health policy makers now have access to a greater number and variety of systematic reviews to inform different stages in the policy making process, including reviews of qualitative research. The inclusion of mixed methods studies in systematic reviews is increasing, but these studies pose particular challenges to methods of review. This article examines the quality of the reporting of mixed methods and qualitative-only studies. We used two completed systematic reviews to generate a sample of qualitative studies and mixed method studies in order to make an assessment of how the quality of reporting and rigor of qualitative-only studies compares with that of mixed-methods studies. Overall, the reporting of qualitative studies in our sample was consistently better when compared with the reporting of mixed methods studies. We found that mixed methods studies are less likely to provide a description of the research conduct or qualitative data analysis procedures and less likely to be judged credible or provide rich data and thick description compared with standalone qualitative studies. Our time-related analysis shows that for both types of study, papers published since 2003 are more likely to report on the study context, describe analysis procedures, and be judged credible and provide rich data. However, the reporting of other aspects of research conduct (i.e. descriptions of the research question, the sampling strategy, and data collection methods) in mixed methods studies does not appear to have improved over time. Mixed methods research makes an important contribution to health research in general, and could make a more substantial contribution to systematic reviews. Through our careful analysis of the quality of reporting of mixed methods and qualitative-only research, we have identified areas that deserve more attention in the conduct and reporting of mixed methods research.

Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews.

PubMed

Shea, Beverley J; Grimshaw, Jeremy M; Wells, George A; Boers, Maarten; Andersson, Neil; Hamel, Candyce; Porter, Ashley C; Tugwell, Peter; Moher, David; Bouter, Lex M

2007-02-15

Our objective was to develop an instrument to assess the methodological quality of systematic reviews, building upon previous tools, empirical evidence and expert consensus. A 37-item assessment tool was formed by combining 1) the enhanced Overview Quality Assessment Questionnaire (OQAQ), 2) a checklist created by Sacks, and 3) three additional items recently judged to be of methodological importance. This tool was applied to 99 paper-based and 52 electronic systematic reviews. Exploratory factor analysis was used to identify underlying components. The results were considered by methodological experts using a nominal group technique aimed at item reduction and design of an assessment tool with face and content validity. The factor analysis identified 11 components. From each component, one item was selected by the nominal group. The resulting instrument was judged to have face and content validity. A measurement tool for the 'assessment of multiple systematic reviews' (AMSTAR) was developed. The tool consists of 11 items and has good face and content validity for measuring the methodological quality of systematic reviews. Additional studies are needed with a focus on the reproducibility and construct validity of AMSTAR, before strong recommendations can be made on its use.

Forty-two systematic reviews generated 23 items for assessing the risk of bias in values and preferences' studies.

PubMed

Yepes-Nuñez, Juan Jose; Zhang, Yuan; Xie, Feng; Alonso-Coello, Pablo; Selva, Anna; Schünemann, Holger; Guyatt, Gordon

2017-05-01

In systematic reviews of studies of patients' values and preferences, the objective of the study was to summarize items and domains authors have identified when considering the risk of bias (RoB) associated with primary studies. We conducted a systematic survey of systematic reviews of patients' values and preference studies. Our search included three databases (MEDLINE, EMBASE, and PsycINFO) from their inception to August 2015. We conducted duplicate data extraction, focusing on items that authors used to address RoB in the primary studies included in their reviews and the associated underlying domains, and summarized criteria in descriptive tables. We identified 42 eligible systematic reviews that addressed 23 items relevant to RoB and grouped the items into 7 domains: appropriate administration of instrument; instrument choice; instrument-described health state presentation; choice of participants group; description, analysis, and presentation of methods and results; patient understanding; and subgroup analysis. The items and domains identified provide insight into issues of RoB in patients' values and preference studies and establish the basis for an instrument to assess RoB in such studies. Copyright © 2017 Elsevier Inc. All rights reserved.

CFHTLenS revisited: assessing concordance with Planck including astrophysical systematics

NASA Astrophysics Data System (ADS)

Joudaki, Shahab; Blake, Chris; Heymans, Catherine; Choi, Ami; Harnois-Deraps, Joachim; Hildebrandt, Hendrik; Joachimi, Benjamin; Johnson, Andrew; Mead, Alexander; Parkinson, David; Viola, Massimo; van Waerbeke, Ludovic

2017-02-01

We investigate the impact of astrophysical systematics on cosmic shear cosmological parameter constraints from the Canada-France-Hawaii Telescope Lensing Survey (CFHTLenS) and the concordance with cosmic microwave background measurements by Planck. We present updated CFHTLenS cosmic shear tomography measurements extended to degree scales using a covariance calibrated by a new suite of N-body simulations. We analyse these measurements with a new model fitting pipeline, accounting for key systematic uncertainties arising from intrinsic galaxy alignments, baryonic effects in the non-linear matter power spectrum, and photometric redshift uncertainties. We examine the impact of the systematic degrees of freedom on the cosmological parameter constraints, both independently and jointly. When the systematic uncertainties are considered independently, the intrinsic alignment amplitude is the only degree of freedom that is substantially preferred by the data. When the systematic uncertainties are considered jointly, there is no consistently strong preference in favour of the more complex models. We quantify the level of concordance between the CFHTLenS and Planck data sets by employing two distinct data concordance tests, grounded in Bayesian evidence and information theory. We find that the two data concordance tests largely agree with one another and that the level of concordance between the CFHTLenS and Planck data sets is sensitive to the exact details of the systematic uncertainties included in our analysis, ranging from decisive discordance to substantial concordance as the treatment of the systematic uncertainties becomes more conservative. The least conservative scenario is the one most favoured by the cosmic shear data, but it is also the one that shows the greatest degree of discordance with Planck. The data and analysis code are publicly available at https://github.com/sjoudaki/cfhtlens_revisited.

Methods to systematically review and meta-analyse observational studies: a systematic scoping review of recommendations.

PubMed

Mueller, Monika; D'Addario, Maddalena; Egger, Matthias; Cevallos, Myriam; Dekkers, Olaf; Mugglin, Catrina; Scott, Pippa

2018-05-21

Systematic reviews and meta-analyses of observational studies are frequently performed, but no widely accepted guidance is available at present. We performed a systematic scoping review of published methodological recommendations on how to systematically review and meta-analyse observational studies. We searched online databases and websites and contacted experts in the field to locate potentially eligible articles. We included articles that provided any type of recommendation on how to conduct systematic reviews and meta-analyses of observational studies. We extracted and summarised recommendations on pre-defined key items: protocol development, research question, search strategy, study eligibility, data extraction, dealing with different study designs, risk of bias assessment, publication bias, heterogeneity, statistical analysis. We summarised recommendations by key item, identifying areas of agreement and disagreement as well as areas where recommendations were missing or scarce. The searches identified 2461 articles of which 93 were eligible. Many recommendations for reviews and meta-analyses of observational studies were transferred from guidance developed for reviews and meta-analyses of RCTs. Although there was substantial agreement in some methodological areas there was also considerable disagreement on how evidence synthesis of observational studies should be conducted. Conflicting recommendations were seen on topics such as the inclusion of different study designs in systematic reviews and meta-analyses, the use of quality scales to assess the risk of bias, and the choice of model (e.g. fixed vs. random effects) for meta-analysis. There is a need for sound methodological guidance on how to conduct systematic reviews and meta-analyses of observational studies, which critically considers areas in which there are conflicting recommendations.

Meta-Analysis: A Systematic Method for Synthesizing Counseling Research

ERIC Educational Resources Information Center

Whiston, Susan C.; Li, Peiwei

2011-01-01

The authors provide a template for counseling researchers who are interested in quantitatively aggregating research findings. Meta-analytic studies can provide relevant information to the counseling field by systematically synthesizing studies performed by researchers from diverse fields. Methodologically sound meta-analyses require careful…

Investigation of a systematic offset in the measurement of organic carbon with a semicontinuous analyzer.

PubMed

Offenberg, John H; Lewandowski, Michael; Edney, Edward O; Kleindienst, Tadeusz E; Jaoui, Mohammed

2007-05-01

Organic carbon (OC) was measured semicontinuously in laboratory experiments of steady-state secondary organic aerosol formed by hydrocarbon + nitrogen oxide irradiations. Examination of the mass of carbon measured on the filter for various sample volumes reveals a systematic offset that is not observed when performing an instrumental blank. These findings suggest that simple subtraction of instrumental blanks determined as the standard analysis without sample collection (i.e., by cycling the pump and valves yet filtering zero liters of air followed by routine chemical analysis) from measured concentrations may be inadequate. This may be especially true for samples collected through the filtration of small air volumes wherein the influence of the systematic offset is greatest. All of the experiments show that filtering a larger volume of air minimizes the influence of contributions from the systematic offset. Application of these results to measurements of ambient concentrations of carbonaceous aerosol suggests a need for collection of sufficient carbon mass to minimize the relative influence of the offset signal.

The role of decision analysis in informed consent: choosing between intuition and systematicity.

PubMed

Ubel, P A; Loewenstein, G

1997-03-01

An important goal of informed consent is to present information to patients so that they can decide which medical option is best for them, according to their values. Research in cognitive psychology has shown that people are rapidly overwhelmed by having to consider more than a few options in making choices. Decision analysis provides a quantifiable way to assess patients' values, and it eliminates the burden of integrating these values with probabilistic information. In this paper we evaluate the relative importance of intuition and systematicity in informed consent. We point out that there is no gold standard for optimal decision making in decisions that hinge on patient values. We also point out that in some such situations it is too early to assume that the benefits of systematicity outweigh the benefits of intuition. Research is needed to address the question of which situations favor the use of intuitive approaches of decision making and which call for a more systematic approach.

Evidence for Cognitive Remediation Therapy in Young People with Anorexia Nervosa: Systematic Review and Meta-analysis of the Literature.

PubMed

Tchanturia, Kate; Giombini, Lucia; Leppanen, Jenni; Kinnaird, Emma

2017-07-01

Cognitive remediation therapy (CRT) for eating disorders has demonstrated promising findings in adult age groups, with randomised treatment trials and systematic reviews demonstrating medium to large effect sizes in improved cognitive performance. In recent years, several case series have been conducted for young people with anorexia nervosa, but these findings have not been synthesised in the form of a systematic review. This systematic review aimed to evaluate the evidence for the efficacy of CRT in child and adolescent age groups. Nine studies were identified, with a subsequent meta-analysis suggesting improvements in cognitive performance with small effect sizes. Patient feedback was positive, with low dropout rates. These findings suggest that CRT has potential as a supplementary treatment for young people with anorexia nervosa, warranting further investigation using randomised treatment trials. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Benzodiazepines for PTSD: A Systematic Review and Meta-Analysis.

PubMed

Guina, Jeffrey; Rossetter, Sarah R; DeRHODES, Bethany J; Nahhas, Ramzi W; Welton, Randon S

2015-07-01

Although benzodiazepines (BZDs) are commonly used in the treatment of posttraumatic stress disorder (PTSD), no systematic review or meta-analysis has specifically examined this treatment. The goal of this study was to analyze and summarize evidence concerning the efficacy of BZDs in treating PTSD. The review protocol was undertaken according to the principles recommended by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and is registered with the PROSPERO international prospective register of systematic reviews (http://www.crd.york.ac.uk/PROSPERO, registration number CRD42014009318). Two authors independently conducted a search of all relevant articles using multiple electronic databases and independently abstracted information from studies measuring PTSD outcomes in patients using BZDs. Eighteen clinical trials and observational studies were identified, with a total of 5236 participants. Outcomes were assessed using qualitative and quantitative syntheses, including meta-analysis. BZDs are ineffective for PTSD treatment and prevention, and risks associated with their use tend to outweigh potential short-term benefits. In addition to adverse effects in general populations, BZDs are associated with specific problems in patients with PTSD: worse overall severity, significantly increased risk of developing PTSD with use after recent trauma, worse psychotherapy outcomes, aggression, depression, and substance use. Potential biopsychosocial explanations for these results are proposed based on studies that have investigated BZDs, PTSD, and relevant animal models. The results of this systematic review suggest that BZDs should be considered relatively contraindicated for patients with PTSD or recent trauma. Evidence-based treatments for PTSD should be favored over BZDs.

The Traditional Chinese Medicine and Relevant Treatment for the Efficacy and Safety of Atopic Dermatitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Shi, Zhao-feng; Song, Tie-bing; Xie, Juan; Yan, Yi-quan

2017-01-01

Background Atopic dermatitis (AD) has become a common skin disease that requires systematic and comprehensive treatment to achieve adequate clinical control. Traditional Chinese medicines and related treatments have shown clinical effects for AD in many studies. But the systematic reviews and meta-analyses for them are lacking. Objective The systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement were conducted to evaluate the efficacy and safety of traditional Chinese medicines and related treatments for AD treatment. Methods Randomized controlled trials (RCTs) were searched based on standardized searching rules in eight medical databases from the inception up to December 2016 and a total of 24 articles with 1,618 patients were enrolled in this meta-analysis. Results The results revealed that traditional Chinese medicines and related treatments did not show statistical differences in clinical effectiveness, SCORAD amelioration, and SSRI amelioration for AD treatment compared with control group. However, EASI amelioration of traditional Chinese medicines and related treatments for AD was superior to control group. Conclusion We need to make conclusion cautiously for the efficacy and safety of traditional Chinese medicine and related treatment on AD therapy. More standard, multicenter, double-blind randomized controlled trials (RCTs) of traditional Chinese medicine and related treatment for AD were required to be conducted for more clinical evidences providing in the future. PMID:28713436

Automating Frame Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanfilippo, Antonio P.; Franklin, Lyndsey; Tratz, Stephen C.

2008-04-01

Frame Analysis has come to play an increasingly stronger role in the study of social movements in Sociology and Political Science. While significant steps have been made in providing a theory of frames and framing, a systematic characterization of the frame concept is still largely lacking and there are no rec-ognized criteria and methods that can be used to identify and marshal frame evi-dence reliably and in a time and cost effective manner. Consequently, current Frame Analysis work is still too reliant on manual annotation and subjective inter-pretation. The goal of this paper is to present an approach to themore » representation, acquisition and analysis of frame evidence which leverages Content Analysis, In-formation Extraction and Semantic Search methods to provide a systematic treat-ment of a Frame Analysis and automate frame annotation.« less

[Applications of meta-analysis in multi-omics].

PubMed

Han, Mingfei; Zhu, Yunping

2014-07-01

As a statistical method integrating multi-features and multi-data, meta-analysis was introduced to the field of life science in the 1990s. With the rapid advances in high-throughput technologies, life omics, the core of which are genomics, transcriptomics and proteomics, is becoming the new hot spot of life science. Although the fast output of massive data has promoted the development of omics study, it results in excessive data that are difficult to integrate systematically. In this case, meta-analysis is frequently applied to analyze different types of data and is improved continuously. Here, we first summarize the representative meta-analysis methods systematically, and then study the current applications of meta-analysis in various omics fields, finally we discuss the still-existing problems and the future development of meta-analysis.

Methodological quality and reporting of systematic reviews in hand and wrist pathology.

PubMed

Wasiak, J; Shen, A Y; Ware, R; O'Donohoe, T J; Faggion, C M

2017-10-01

The objective of this study was to assess methodological and reporting quality of systematic reviews in hand and wrist pathology. MEDLINE, EMBASE and Cochrane Library were searched from inception to November 2016 for relevant studies. Reporting quality was evaluated using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and methodological quality using a measurement tool to assess systematic reviews, the Assessment of Multiple Systematic Reviews (AMSTAR). Descriptive statistics and linear regression were used to identify features associated with improved methodological quality. A total of 91 studies were included in the analysis. Most reviews inadequately reported PRISMA items regarding study protocol, search strategy and bias and AMSTAR items regarding protocol, publication bias and funding. Systematic reviews published in a plastics journal, or which included more authors, were associated with higher AMSTAR scores. A large proportion of systematic reviews within hand and wrist pathology literature score poorly with validated methodological assessment tools, which may affect the reliability of their conclusions. I.

From Genomics to Omics Landscapes of Parkinson's Disease: Revealing the Molecular Mechanisms

PubMed Central

Redenšek, Sara; Dolžan, Vita

2018-01-01

Abstract Molecular mechanisms of Parkinson's disease (PD) have already been investigated in various different omics landscapes. We reviewed the literature about different omics approaches between November 2005 and November 2017 to depict the main pathological pathways for PD development. In total, 107 articles exploring different layers of omics data associated with PD were retrieved. The studies were grouped into 13 omics layers: genomics–DNA level, transcriptomics, epigenomics, proteomics, ncRNomics, interactomics, metabolomics, glycomics, lipidomics, phenomics, environmental omics, pharmacogenomics, and integromics. We discussed characteristics of studies from different landscapes, such as main findings, number of participants, sample type, methodology, and outcome. We also performed curation and preliminary synthesis of multiple omics data, and identified overlapping results, which could lead toward selection of biomarkers for further validation of PD risk loci. Biomarkers could support the development of targeted prognostic/diagnostic panels as a tool for early diagnosis and prediction of progression rate and prognosis. This review presents an example of a comprehensive approach to revealing the underlying processes and risk factors of a complex disease. It urges scientists to structure the already known data and integrate it into a meaningful context. PMID:29356624

Gene-gene and gene-environment interactions: new insights into the prevention, detection and management of coronary artery disease.

PubMed

Lanktree, Matthew B; Hegele, Robert A

2009-02-26

Despite the recent success of genome-wide association studies (GWASs) in identifying loci consistently associated with coronary artery disease (CAD), a large proportion of the genetic components of CAD and its metabolic risk factors, including plasma lipids, type 2 diabetes and body mass index, remain unattributed. Gene-gene and gene-environment interactions might produce a meaningful improvement in quantification of the genetic determinants of CAD. Testing for gene-gene and gene-environment interactions is thus a new frontier for large-scale GWASs of CAD. There are several anecdotal examples of monogenic susceptibility to CAD in which the phenotype was worsened by an adverse environment. In addition, small-scale candidate gene association studies with functional hypotheses have identified gene-environment interactions. For future evaluation of gene-gene and gene-environment interactions to achieve the same success as the single gene associations reported in recent GWASs, it will be important to pre-specify agreed standards of study design and statistical power, environmental exposure measurement, phenomic characterization and analytical strategies. Here we discuss these issues, particularly in relation to the investigation and potential clinical utility of gene-gene and gene-environment interactions in CAD.

Limits of the copper decoration technique for delineating of the V I boundary

NASA Astrophysics Data System (ADS)

Válek, L.; Stehlík, Š.; Orava, J.; Ďurík, M.; Šik, J.; Wágner, T.

2007-05-01

Copper decoration technique was used for detection of the vacancy interstitial (V I) boundary in Czochralski silicon crystal. We used the technique for delineating defects in silicon previously reported by Mule’Stagno [Solid State Phenom. 82 84 (2002) 753] and we enriched it by an upgraded application of copper on the silicon surface. The new procedure is based on the deposition of elementary copper on the silicon surface from the copper nitrate solution. The new method is more efficient contrary to Mule’Stagno (2002) and it also decreases environmental drain. We compared five etchants in order to optimize the delineation of the V I boundary. A defect region of the same diameter was detected by all the used etchants, supreme sensitivity was obtained with Wright's etchant. The outer diameter of the defect region observed by the copper decoration technique coincides with the V I boundary diameter measured by OISF testing and approximately coincides with the V I boundary diameter measured by COP testing. We found that the copper decoration technique delineates oxygen precipitates in silicon and we observed the dependence of V I boundary detectability on the size of the oxygen precipitates.

Comparative phenomics and targeted use of genomics reveals variation in carbon and nitrogen assimilation among different Brettanomyces bruxellensis strains.

PubMed

Crauwels, S; Van Assche, A; de Jonge, R; Borneman, A R; Verreth, C; Troels, P; De Samblanx, G; Marchal, K; Van de Peer, Y; Willems, K A; Verstrepen, K J; Curtin, C D; Lievens, B

2015-11-01

Recent studies have suggested a correlation between genotype groups of Brettanomyces bruxellensis and their source of isolation. To further explore this relationship, the objective of this study was to assess metabolic differences in carbon and nitrogen assimilation between different B. bruxellensis strains from three beverages, including beer, wine, and soft drink, using Biolog Phenotype Microarrays. While some similarities of physiology were noted, many traits were variable among strains. Interestingly, some phenotypes were found that could be linked to strain origin, especially for the assimilation of particular α- and β-glycosides as well as α- and β-substituted monosaccharides. Based upon gene presence or absence, an α-glucosidase and β-glucosidase were found explaining the observed phenotypes. Further, using a PCR screen on a large number of isolates, we have been able to specifically link a genomic deletion to the beer strains, suggesting that this region may have a fitness cost for B. bruxellensis in certain fermentation systems such as brewing. More specifically, none of the beer strains were found to contain a β-glucosidase, which may have direct impacts on the ability for these strains to compete with other microbes or on flavor production.

Personalized medicine: from genotypes, molecular phenotypes and the quantified self, towards improved medicine.

PubMed

Dudley, Joel T; Listgarten, Jennifer; Stegle, Oliver; Brenner, Steven E; Parts, Leopold

2015-01-01

Advances in molecular profiling and sensor technologies are expanding the scope of personalized medicine beyond genotypes, providing new opportunities for developing richer and more dynamic multi-scale models of individual health. Recent studies demonstrate the value of scoring high-dimensional microbiome, immune, and metabolic traits from individuals to inform personalized medicine. Efforts to integrate multiple dimensions of clinical and molecular data towards predictive multi-scale models of individual health and wellness are already underway. Improved methods for mining and discovery of clinical phenotypes from electronic medical records and technological developments in wearable sensor technologies present new opportunities for mapping and exploring the critical yet poorly characterized "phenome" and "envirome" dimensions of personalized medicine. There are ambitious new projects underway to collect multi-scale molecular, sensor, clinical, behavioral, and environmental data streams from large population cohorts longitudinally to enable more comprehensive and dynamic models of individual biology and personalized health. Personalized medicine stands to benefit from inclusion of rich new sources and dimensions of data. However, realizing these improvements in care relies upon novel informatics methodologies, tools, and systems to make full use of these data to advance both the science and translational applications of personalized medicine.

Supervised segmentation of phenotype descriptions for the human skeletal phenome using hybrid methods.

PubMed

Groza, Tudor; Hunter, Jane; Zankl, Andreas

2012-10-15

Over the course of the last few years there has been a significant amount of research performed on ontology-based formalization of phenotype descriptions. In order to fully capture the intrinsic value and knowledge expressed within them, we need to take advantage of their inner structure, which implicitly combines qualities and anatomical entities. The first step in this process is the segmentation of the phenotype descriptions into their atomic elements. We present a two-phase hybrid segmentation method that combines a series individual classifiers using different aggregation schemes (set operations and simple majority voting). The approach is tested on a corpus comprised of skeletal phenotype descriptions emerged from the Human Phenotype Ontology. Experimental results show that the best hybrid method achieves an F-Score of 97.05% in the first phase and F-Scores of 97.16% / 94.50% in the second phase. The performance of the initial segmentation of anatomical entities and qualities (phase I) is not affected by the presence / absence of external resources, such as domain dictionaries. From a generic perspective, hybrid methods may not always improve the segmentation accuracy as they are heavily dependent on the goal and data characteristics.

How Effective are Mindfulness-Based Interventions for Reducing Stress Among Healthcare Professionals? A Systematic Review and Meta-Analysis.

PubMed

Burton, Amy; Burgess, Catherine; Dean, Sarah; Koutsopoulou, Gina Z; Hugh-Jones, Siobhan

2017-02-01

Workplace stress is high among healthcare professionals (HCPs) and is associated with reduced psychological health, quality of care and patient satisfaction. This systematic review and meta-analysis reviews evidence on the effectiveness of mindfulness-based interventions (MBIs) for reducing stress in HCPs. A systematic literature search was conducted. Papers were screened for suitability using inclusion criteria and nine papers were subjected to review and quality assessment. Seven papers, for which full statistical findings could be obtained, were also subjected to meta-analysis. Results of the meta-analysis suggest that MBIs have the potential to significantly improve stress among HCPs; however, there was evidence of a file drawer problem. The quality of the studies was high in relation to the clarity of aims, data collection and analysis, but weaker in terms of sample size and the use of theoretical frameworks. MBIs have the potential to reduce stress among HCPs; however, more high-quality research is needed before this finding can be confirmed. Future studies would benefit from long-term follow-up measures to determine any continuing effects of mindfulness training on stress outcomes. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Subclinical hypothyroidism: to treat or not to treat, that is the question! A systematic review with meta-analysis on lipid profile

PubMed Central

Lau, Eva; de Sousa Pinto, Bernardo; Carvalho, Davide

2017-01-01

Previous studies suggested that subclinical hypothyroidism has a detrimental effect on cardiovascular risk factors, and that its effective treatment may have a beneficial impact on overall health. The main purpose of this review and meta-analysis was to assess whether subclinical hypothyroidism treatment is of clinical relevance, based on cardiovascular risk parameters correction. A systemic research of the literature using MEDLINE tool was performed to identify the relevant studies. Only placebo-controlled randomized control trials were included. A quantitative analysis was also performed. This systematic review and meta-analysis of randomized placebo-controlled trials assess the different impact of levothyroxine vs placebo treatment. A significant decrease in serum thyroid-stimulating hormone and total and low-density lipoprotein cholesterol was obtained with levothyroxine therapy (66, 9 and 14%, respectively) and, although modest, this could be significant in terms of reduction of the incidence of coronary artery disease. Other significant results of lipid parameters were not obtained. This systematic review provides a strong evidence-based data in favour of specific changes and beneficial effects of levothyroxine treatment. PMID:28249936

A Review of Dendroctonus frontalis Zimmermann Systematics

Treesearch

Anthony I. Cognato

2011-01-01

The systematic history of the southern pine beetle, Dendroctonus frontalis Zimmermann, is reviewed. Morphological, biological, karyological, and molecular data clearly define and diagnose the species limits of D. frontalis. More complete phylogenetic analysis and characterization of population genetic variation will further clarify the evolutionary history of the D....

The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline: a systematic review.

PubMed

Zeng, Xiantao; Zhang, Yonggang; Kwong, Joey S W; Zhang, Chao; Li, Sheng; Sun, Feng; Niu, Yuming; Du, Liang

2015-02-01

To systematically review the methodological assessment tools for pre-clinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline. We searched PubMed, the Cochrane Handbook for Systematic Reviews of Interventions, Joanna Briggs Institute (JBI) Reviewers Manual, Centre for Reviews and Dissemination, Critical Appraisal Skills Programme (CASP), Scottish Intercollegiate Guidelines Network (SIGN), and the National Institute for Clinical Excellence (NICE) up to May 20th, 2014. Two authors selected studies and extracted data; quantitative analysis was performed to summarize the characteristics of included tools. We included a total of 21 assessment tools for analysis. A number of tools were developed by academic organizations, and some were developed by only a small group of researchers. The JBI developed the highest number of methodological assessment tools, with CASP coming second. Tools for assessing the methodological quality of randomized controlled studies were most abundant. The Cochrane Collaboration's tool for assessing risk of bias is the best available tool for assessing RCTs. For cohort and case-control studies, we recommend the use of the Newcastle-Ottawa Scale. The Methodological Index for Non-Randomized Studies (MINORS) is an excellent tool for assessing non-randomized interventional studies, and the Agency for Healthcare Research and Quality (ARHQ) methodology checklist is applicable for cross-sectional studies. For diagnostic accuracy test studies, the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool is recommended; the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool is available for assessing animal studies; Assessment of Multiple Systematic Reviews (AMSTAR) is a measurement tool for systematic reviews/meta-analyses; an 18-item tool has been developed for appraising case series studies, and the Appraisal of Guidelines, Research and Evaluation (AGREE)-II instrument is widely used to evaluate clinical practice guidelines. We have successfully identified a variety of methodological assessment tools for different types of study design. However, further efforts in the development of critical appraisal tools are warranted since there is currently a lack of such tools for other fields, e.g. genetic studies, and some existing tools (nested case-control studies and case reports, for example) are in need of updating to be in line with current research practice and rigor. In addition, it is very important that all critical appraisal tools remain subjective and performance bias is effectively avoided. © 2015 Chinese Cochrane Center, West China Hospital of Sichuan University and Wiley Publishing Asia Pty Ltd.

The application of knowledge synthesis methods in agri-food public health: recent advancements, challenges and opportunities.

PubMed

Young, Ian; Waddell, Lisa; Sanchez, Javier; Wilhelm, Barbara; McEwen, Scott A; Rajić, Andrijana

2014-03-01

Knowledge synthesis refers to the integration of findings from individual research studies on a given topic or question into the global knowledge base. The application of knowledge synthesis methods, particularly systematic reviews and meta-analysis, has increased considerably in the agri-food public health sector over the past decade and this trend is expected to continue. The objectives of our review were: (1) to describe the most promising knowledge synthesis methods and their applicability in agri-food public health, and (2) to summarize the recent advancements, challenges, and opportunities in the use of systematic review and meta-analysis methods in this sector. We performed a structured review of knowledge synthesis literature from various disciplines to address the first objective, and used comprehensive insights and experiences in applying these methods in the agri-food public health sector to inform the second objective. We describe five knowledge synthesis methods that can be used to address various agri-food public health questions or topics under different conditions and contexts. Scoping reviews describe the main characteristics and knowledge gaps in a broad research field and can be used to evaluate opportunities for prioritizing focused questions for related systematic reviews. Structured rapid reviews are streamlined systematic reviews conducted within a short timeframe to inform urgent decision-making. Mixed-method and qualitative reviews synthesize diverse sources of contextual knowledge (e.g. socio-cognitive, economic, and feasibility considerations). Systematic reviews are a structured and transparent method used to summarize and synthesize literature on a clearly-defined question, and meta-analysis is the statistical combination of data from multiple individual studies. We briefly describe and discuss key advancements in the use of systematic reviews and meta-analysis, including: risk-of-bias assessments; an overall quality-of-evidence approach; engagement of stakeholders; Bayesian, multivariate, and network meta-analysis; and synthesis of diagnostic test accuracy studies. We also highlight several challenges and opportunities in the conduct of systematic reviews (e.g. inclusion of grey literature, minimizing language bias, and optimizing search strategies) and meta-analysis (e.g. inclusion of observational studies and approaches to address the insufficient reporting of data and significant heterogeneity). Many of these developments have yet to be comprehensively applied and evaluated in an agri-food public health context, and more research is needed in this area. There is a need to strengthen knowledge synthesis capacity and infrastructure at the regional, national, and international levels in this sector to ensure that the best available knowledge is used to inform future decision-making about agri-food public health issues. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Systematic analysis of EOS data system for operations

NASA Technical Reports Server (NTRS)

Moe, K. L.; Dasgupta, R.

1985-01-01

A data management analysis methodology is being proposed. The objective of the methodology is to assist mission managers by identifying a series of ordered activities to be systematically followed in order to arrive at an effective ground system design. Existing system engineering tools and concepts have been assembled into a structured framework to facilitate the work of a mission planner. It is intended that this methodology can be gainfully applied (with probable modifications and/or changes) to the EOS payloads and their associated data systems.

Long-term Use of the Sialogogue Medications Pilocarpine and Cevimeline Can Reduce Xerostomia Symptoms and Increase Salivary Flow in Head and Neck Cancer Survivors After Radiotherapy.

PubMed

Barbe, Anna Greta

2017-09-01

Interventions for the management of radiotherapy-induced xerostomia and hyposalivation: A systematic review and meta-analysis. Mercadante V, Hamad AA, Lodi G, Porter S, Fedele S. Oral Oncol 2017;66:64-74. The authors reported that no external funding sources directly supported this study TYPE OF STUDY/DESIGN: Systematic review and meta-analysis. Copyright © 2017 Elsevier Inc. All rights reserved.

Oxytocin and brain activity in humans: A systematic review and coordinate-based meta-analysis of functional MRI studies.

PubMed

Grace, Sally A; Rossell, Susan L; Heinrichs, Markus; Kordsachia, Catarina; Labuschagne, Izelle

2018-05-24

Oxytocin (OXT) is a neuropeptide which has a critical role in human social behaviour and cognition. Research investigating the role of OXT on functional brain changes in humans has often used task paradigms that probe socioemotional processes. Preliminary evidence suggests a central role of the amygdala in the social cognitive effects of intranasal OXT (IN-OXT), however, inconsistencies in task-design and analysis methods have led to inconclusive findings regarding a cohesive model of the neural mechanisms underlying OXT's actions. The aim of this meta-analysis was to systematically investigate these findings. A systematic search of PubMed, PsycINFO, and Scopus databases was conducted for fMRI studies which compared IN-OXT to placebo in humans. First, we systematically reviewed functional magnetic resonance imaging (fMRI) studies of IN-OXT, including studies of healthy humans, those with clinical disorders, and studies examining resting-state fMRI (rsfMRI). Second, we employed a coordinate-based meta-analysis for task-based neuroimaging literature using activation likelihood estimation (ALE), whereby, coordinates were extracted from clusters with significant differences in IN-OXT versus placebo in healthy adults. Data were included for 39 fMRI studies that reported a total of 374 distinct foci. The meta-analysis identified task-related IN-OXT increases in activity within a cluster of the left superior temporal gyrus during tasks of emotion processing. These findings are important as they implicate regions beyond the amygdala in the neural effects of IN-OXT. The outcomes from this meta-analysis can guide a priori predictions for future OXT research, and provide an avenue for targeted treatment interventions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Meta-analysis and systematic review of studies on the effectiveness of HIV stigma reduction programs.

PubMed

Mak, Winnie W S; Mo, Phoenix K H; Ma, Gloria Y K; Lam, Maggie Y Y

2017-09-01

The present study conducted a meta-analysis and systematic review on studies evaluating the effectiveness of stigma reduction programs in improving knowledge and reducing negative attitudes towards people living with HIV (PLHIV). Meta-analysis (k = 42 studies) found significant and small effect sizes in the improvement of the participants' knowledge of HIV/AIDS from interventions with (Cohen's d = 0.48, 95% CI [0.30, 0.66]) and without control groups (Cohen's d = 0.42, 95% CI [0.28, 0.57]). Significant and small effect sizes were found in the improvement of the participants' attitudes toward PLHIV from interventions with (Cohen's d = 0.39, 95% CI [0.23, 0.55]) and without control groups (Cohen's d = 0.25, 95% CI [0.11, 0.39]). Significant and small effect sizes were sustained at the follow-up assessments. Subgroup analysis showed that number of intervention sessions, intervention settings, and sample type significantly moderated the effect sizes in the meta-analysis. Findings from the systematic review of 35 studies indicated that most of the included studies showed positive results in reducing negative attitudes toward PLHIV and improving HIV-related knowledge. Most of the included studies tended to have low methodological quality. The present meta-analysis and systematic review indicated that the studies generally found small improvement in HIV-related knowledge and reduction in negative attitudes towards PLHIV among the stigma reduction programs being evaluated. High-quality stigma reduction programs with multidimensional stigma indicators and psychometrically sound outcome measures are highly warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mobile Phone Apps to Promote Weight Loss and Increase Physical Activity: A Systematic Review and Meta-Analysis.

PubMed

Flores Mateo, Gemma; Granado-Font, Esther; Ferré-Grau, Carme; Montaña-Carreras, Xavier

2015-11-10

To our knowledge, no meta-analysis to date has assessed the efficacy of mobile phone apps to promote weight loss and increase physical activity. To perform a systematic review and meta-analysis of studies to compare the efficacy of mobile phone apps compared with other approaches to promote weight loss and increase physical activity. We conducted a systematic review and meta-analysis of relevant studies identified by a search of PubMed, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Scopus from their inception through to August 2015. Two members of the study team (EG-F, GF-M) independently screened studies for inclusion criteria and extracted data. We included all controlled studies that assessed a mobile phone app intervention with weight-related health measures (ie, body weight, body mass index, or waist circumference) or physical activity outcomes. Net change estimates comparing the intervention group with the control group were pooled across studies using random-effects models. We included 12 articles in this systematic review and meta-analysis. Compared with the control group, use of a mobile phone app was associated with significant changes in body weight (kg) and body mass index (kg/m(2)) of -1.04 kg (95% CI -1.75 to -0.34; I2 = 41%) and -0.43 kg/m(2) (95% CI -0.74 to -0.13; I2 = 50%), respectively. Moreover, a nonsignificant difference in physical activity was observed between the two groups (standardized mean difference 0.40, 95% CI -0.07 to 0.87; I2 = 93%). These findings were remarkably robust in the sensitivity analysis. No publication bias was shown. Evidence from this study shows that mobile phone app-based interventions may be useful tools for weight loss.

How arbitrary is language?

PubMed Central

Monaghan, Padraic; Shillcock, Richard C.; Christiansen, Morten H.; Kirby, Simon

2014-01-01

It is a long established convention that the relationship between sounds and meanings of words is essentially arbitrary—typically the sound of a word gives no hint of its meaning. However, there are numerous reported instances of systematic sound–meaning mappings in language, and this systematicity has been claimed to be important for early language development. In a large-scale corpus analysis of English, we show that sound–meaning mappings are more systematic than would be expected by chance. Furthermore, this systematicity is more pronounced for words involved in the early stages of language acquisition and reduces in later vocabulary development. We propose that the vocabulary is structured to enable systematicity in early language learning to promote language acquisition, while also incorporating arbitrariness for later language in order to facilitate communicative expressivity and efficiency. PMID:25092667

Prevalence of antepartum hemorrhage in women with placenta previa: a systematic review and meta-analysis

PubMed Central

Fan, Dazhi; Wu, Song; Liu, Li; Xia, Qing; Wang, Wen; Guo, Xiaoling; Liu, Zhengping

2017-01-01

Antepartum hemorrhage (APH) is an important cause of perinatal mortality and maternal morbidity in pregnant women with placenta previa in the world. However, the epidemiological characteristics are not completely understood. We performed an initial systematic review and meta-analysis to assess the prevalence of APH in pregnant women with placenta previa. It was totally performed following the Preferred Reporting Items for Systematic reviews and Meta-Analysis statement. PubMed, Elsevier Science Direct, and the Cochrane Library were searched before April 2016. A meta-analysis with a random-effects model based on a proportions approach was performed to determine the prevalence. Stratified analyses, meta-regression method, and sensitivity analysis were utilized to analyze the heterogeneity. A total of 29 articles were included. The pooled overall prevalence of APH among pregnant women with placenta previa was 51.6% (95% CI 42.7–60.6) in a heterogeneous set of studies (I2 = 97.9). Correlation analysis found that there was a positive correlation between prevalence and percentage of multiparous (r = 0.534, P = 0.027) and a negative correlation between prevalence and survey year (r = −0.400, P = 0.031). In conclusion, the prevalence of APH was a high condition among pregnant women with placenta previa. PMID:28067303

Dacron® vs. PTFE as bypass materials in peripheral vascular surgery – systematic review and meta-analysis

PubMed Central

Roll, Stephanie; Müller-Nordhorn, Jacqueline; Keil, Thomas; Scholz, Hans; Eidt, Daniela; Greiner, Wolfgang; Willich, Stefan N

2008-01-01

Background In peripheral vascular bypass surgery different synthetic materials are available for bypass grafting. It is unclear which of the two commonly used materials, polytetrafluoroethylene (PTFE) or polyester (Dacron®) grafts, is to be preferred. Thus, the aim of this meta-analysis and systematic review was to compare the effectiveness of these two prosthetic bypass materials (Dacron® and PTFE). Methods We performed a systematic literature search in MEDLINE, Cochrane-Library – CENTRAL, EMBASE and other databases for relevant publications in English and German published between 1999 and 2008. Only randomized controlled trials were considered for inclusion. We assessed the methodological quality by means of standardized checklists. Primary patency was used as the main endpoint. Random-effect meta-analysis as well as pooling data in life table format was performed to combine study results. Results Nine randomized controlled trials (RCT) were included. Two trials showed statistically significant differences in primary patency, one favouring Dacron® and one favouring PTFE grafts, while 7 trials did not show statistically significant differences between the two materials. Meta-analysis on the comparison of PTFE vs. Dacron® grafts yielded no differences with regard to primary patency rates (hazard ratio 1.04 (95% confidence interval [0.85;1.28]), no significant heterogeneity (p = 0.32, I2 = 14%)). Similarly, there were no significant differences with regard to secondary patency rates. Conclusion Systematic evaluation and meta-analysis of randomized controlled trials comparing Dacron® and PTFE as bypass materials for peripheral vascular surgery showed no evidence of an advantage of one synthetic material over the other. PMID:19099583

Endoscopic versus surgical treatment of ampullary adenomas: a systematic review and meta-analysis

PubMed Central

Mendonça, Ernesto Quaresma; Bernardo, Wanderley Marques; de Moura, Eduardo Guimarães Hourneaux; Chaves, Dalton Marques; Kondo, André; Pu, Leonardo Zorrón Cheng Tao; Baracat, Felipe Iankelevich

2016-01-01

The aim of this study is to address the outcomes of endoscopic resection compared with surgery in the treatment of ampullary adenomas. A systematic review and meta-analysis were performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. For this purpose, the Medline, Embase, Cochrane, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Scopus and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases were scanned. Studies included patients with ampullary adenomas and data considering endoscopic treatment compared with surgery. The entire analysis was based on a fixed-effects model. Five retrospective cohort studies were selected (466 patients). All five studies (466 patients) had complete primary resection data available and showed a difference that favored surgical treatment (risk difference [RD] = -0.24, 95% confidence interval [CI] = -0.44 to -0.04). Primary success data were identified in all five studies as well. Analysis showed that the surgical approach outperformed endoscopic treatment for this outcome (RD = -0.37, 95% CI = -0.50 to -0.24). Recurrence data were found in all studies (466 patients), with a benefit indicated for surgical treatment (RD = 0.10, 95% CI = -0.01 to 0.19). Three studies (252 patients) presented complication data, but analysis showed no difference between the approaches for this parameter (RD = -0.15, 95% CI = -0.53 to 0.23). Considering complete primary resection, primary success and recurrence outcomes, the surgical approach achieves significantly better results. Regarding complication data, this systematic review concludes that rates are not significantly different. PMID:26872081

Need for Systematic Retrofit Analysis in Multifamily Buildings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malhotra, Mini; Im, Piljae

2014-01-01

Multifamily housing offers high potential for energy savings through retrofits. A comprehensive energy audit with systematic evaluation of alternative energy measures is one of the key steps to realizing the full energy savings potential. However, this potential often remains unrealized when the selection of measures is (1) based on a one-size-fits-all approach originating from accustomed practices, (2) intended merely to meet code-compliance requirements, and/or (3) influenced by owner renter split incentive. In such cases, the benefits of comprehensive energy auditing are disregarded in view of the apparent difficulty in diagnosing multifamily buildings, evaluating alternative measures, and installing customized sets ofmore » measures. This paper highlights some of the barriers encountered in a multifamily housing retrofit project in Georgia and demonstrates the merits of systematic retrofit analysis by identifying opportunities for higher energy savings and improved comfort and indoor air quality that were missed in this project. The study uses a whole-building energy analysis conducted for a 10-unit, low-rise, multifamily building of a 110-unit apartment complex. The analysis projected a 24% energy savings from the measures installed in the building with a payback period of 10 years. Further analysis with a systematic evaluation of alternative measures showed that without compromising on the objectives of durability, livability, and appearance of the building, energy savings of up to 34% were achievable with a payback period of 7 years. The paper concludes by outlining recommendations that may benefit future retrofit projects by improving the audit process, streamlining tasks, and achieving higher energy savings.« less

Single balloon versus double balloon bipedicular kyphoplasty: a systematic review and meta-analysis.

PubMed

Jing, Zehao; Dong, Jianli; Li, Zhengwei; Nan, Feng

2018-06-19

Kyphoplasty has been widely used to treat vertebral compression fractures (VCFs). In standard procedure of kyphoplasty, two balloons were inserted into the vertebral body through bipedicular and inflated simultaneously, while using a single balloon two times is also a common method in clinic to lessen the financial burden of patients. However, the effect and safety of single balloon versus double balloon bipedicular kyphoplasty are still controversy. In this systematic review and meta-analysis, eligible studies were identified through a comprehensive literature search of PubMed, Cochrane library EMBASE, Web of Science, Wanfang, CNKI, VIP and CBM until January 1, 2018. Results from individual studies were pooled using a random or fixed effects model. Seven articles were included in the systematic review and five studies were consisted in meta-analysis. We observed no significant difference between single balloon and double balloon bipedicular kyphoplasty in visual analog scale (VAS), angle (kyphotic angle and Cobb angle), consumption (operation time, cement volume and volume of bleeding), vertebral height (anterior height, medium height and posterior height) and complications (cement leakage and new VCFs), while the cost of single balloon bipedicular kyphoplasty is lower than that of double balloon bipedicular kyphoplasty. The results of our meta-analysis also demonstrated that single balloon can significantly improve the VAS, angle and vertebral height of patients suffering from VCFs. This systematic review and meta-analysis collectively concludes that single balloon bipedicular kyphoplasty is as effective as double balloon bipedicular kyphoplasty in improving clinical symptoms, deformity and complications of VCFs but not so expensive. These slides can be retrieved under Electronic Supplementary Material.

Dietary patterns and risk of colorectal adenoma: a systematic review and meta-analysis of observational studies.

PubMed

Godos, J; Bella, F; Torrisi, A; Sciacca, S; Galvano, F; Grosso, G

2016-12-01

Current evidence suggests that dietary patterns may play an important role in colorectal cancer risk. The present study aimed to perform a systematic review and meta-analysis of observational studies exploring the association between dietary patterns and colorectal adenomas (a precancerous condition). Pubmed and EMBASE electronic databases were systematically searched to retrieve eligible studies. Only studies exploring the risk or association with colorectal adenomas for the highest versus lowest category of exposure to a posteriori dietary patterns were included in the quantitative analysis. Random-effects models were applied to calculate relative risks (RRs) of colorectal adenomas for high adherence to healthy or unhealthy dietary patterns. Statistical heterogeneity and publication bias were explored. Twelve studies were reviewed. Three studies explored a priori dietary patterns using scores identifying adherence to the Mediterranean, Paleolithic and Dietary Approaches to Stop Hypertension (DASH) diet and reported an association with decreased colorectal adenoma risk. Two studies tested the association with colorectal adenomas between a posteriori dietary patterns showing lower odds of disease related to plant-based compared to meat-based dietary patterns. Seven studies identified 23 a posteriori dietary patterns and the analysis revealed that higher adherence to healthy and unhealthy dietary patterns was significantly associated risk of colorectal adenomas (RR = 0.81, 95% confidence interval = 0.71, 0.94 and RR = 1.24, 95% confidence interval = 1.13, 1.35, respectively) with no evidence of heterogeneity or publication bias. The results of this systematic review and meta-analysis indicate that dietary patterns may be associated with the risk of colorectal adenomas. © 2016 The British Dietetic Association Ltd.